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Behavior Karen L. Overall, MA, VMD, PhD Diplomate ACVB, ABS Certified Applied Animal Behaviorist University of Pennsylvania School of Medicine Neurotransmitter Functions in Pharmacology All client handouts in these notes are from: Overall, KL. Manual of Clinical Behavioral Medicine for Dogs and Cats. Elsevier, St. Louis, 2010. Rationale The addition of psychotherapeutic agents to routine behavioral treatments, such as behavioral and environmental modification, has lead to better and faster treatment outcomes. In addition to facilitating better treatment of domestic animals and humans, psychopharmacological developments have permitted hypotheses about underlying mechanistic pathology to be tested. Mere treatment of non-specific behavioral complaints and signs is outdated (eg., treat barking by cutting the vocal cords) and has been replaced with an approach that includes ensuring that you meet the criteria for diagnosis, prior to treatment, followed by treatment that addresses the specific mechanism underlying the neurochemical contribution to the pathology (1). The use of medication should occur and is most effective as part of an integrated treatment program. There is no substitute for the hard work involved in behavior modification; however, some medications may be able to make it easier to implement the modification (2-4). Those seeking 'quick fix' solutions will doubtless be disappointed: inappropriate drug use will not alter the processes or environments that produced the behavior. While medication, alone, may render an animal globally less anxious, if the animal is still being provoked my social or physical environmental stimuli the benefit of treatment with medication will be minimized. It is partly this facile and inappropriate use of medication that has led many practitioners to falsely believe that medication does not work. Nothing could be further from the truth: the newer serotonin-affecting medications, protective neutraceutical, and enhanced dietary regimes have a huge potential improve life for troubled pets and their distressed people. In fact, rational drug use should now minimally be considered part of basic humane treatment of our patients. Adverse effects The neurotransmitters affected by behavioral medications are acetylcholine, serotonin, norepinephrine (noradrenaline), dopamine, gamma amino butyric acid (GABA), and excitatory amino acids. Common adverse effects of psychotherapeutic drugs are usually caused by a blockage of the muscarinic acetylcholine receptors, which have diffuse connections throughout the brain. These 'common' side effects are actually quite rare and generally manifest themselves as transient changes in GI function or heart rate. If these side effect ARE NOT transient, clients need to understand that their pet may be experiencing a serious problem. For this reason, it is important to encourage clients to help monitor both their anima;'s response to the medication, and any side effects that they may have. Clients can easily learn to take pulse rates. Slight increases in pulse rate when treated with any medications affecting norepinephrine - as most the anti-anxiety agents do - are not worrisome. Huge, sustained increases are problematic. If clients know that their dog's resting heart rate is 65 bpm and with medication this changes to 150 bpm, they can immediately bring this change to their vet's attention. Likewise, if the increase is minor (65 to 75 bpm) they can relax and not worry. Educated clients will monitor their pets better, will be more willing to use medications and behavior mod appropriately, and will also be less likely to take the veterinarian's time needlessly. While many benzodiazepines (BZ) can be sedative, newer BZ have decreased sedative effects. Still, because dogs and cats, like humans, can experience a huge range of effects when given a BZ, clients should be encouraged to give any BZ when they can monitor the patient. This practice is extremely helpful in ensuring that we recognize animals with atypical or serious sedative responses so that we can find more appropriate medications with which to treat them. Most behavioral drugs are metabolized through renal and hepatic pathways so knowledge of baseline values is essential. That said, these medications can be used in compromised animals if adjustments are made and the animal is monitored behaviorally and biochemically. All psychotropic medications can interact with other medications. For example, use of most anti-anxiety agents will cause thyroidal values - whether or not supplementation is involved - for read falsely low. Many of serotnergic agents are thought to lower seizure thresholds and so are recommended with caution in patients treated with seizures. That said, there is now evidence in both the human and canine literature that anxiety may lower seizure thresholds and so treatment of the anxiety may allow the patient to successfully decrease the amount of seizure medication needed. Efficacy and mechanism of action It's important for clients to understand that newer, more specific, more efficacious drugs have a relatively long lag time between initiation of treatment and apparent changes in the patient's behavior. This delay is due to the mechanism of action of the tricyclic antidepressants (TCAs) and the selective serotonin re-uptake inhibitors (SSRIs) which employ second messenger systems to alter transcription of receptor proteins. Serotonin Serotonin (5-HT) receptors are all G-protein-coupled receptors. There are 14 identified classes of serotonin receptors. The 5-HT1 receptors are linked to the inhibition of adenylate cyclase and affect mood and behavior. Presynaptic 5-HT1A-receptors predominate in dorsal and median raphé nuclei; post-synaptic 5-HT1A-receptors predominant in limbic regions (hippocampus and septum) and some cortical layers. Activation of pre-synaptic receptors by agonists results in decreased firing of serotonergic neurons leading to transient suppression of 5-HT synthesis and decreased 5-HT release; activation of post-synaptic receptors decreases firing of post-synaptic cells. These are 'thermostatic' effects, not integrated outcomes of receptor activation. The overall effect depends on regulation of second messengers (cAMP, Ca2+, cGMP, IP3) and their effects on protein kinases which then alter neuronal metabolism and receptor protein transcription (5). The subclasses of 5-HT receptors vary in their affects. 5-HT1A receptors affect mood and behavior. 5-HT1D receptors affect cerebral blood vessels and appear to be involved in the development of migraine. These last two classes of receptor subtypes are the primary focus of many behavioral drugs. Urinary excretion of 5-HIAA (5-hydroxy indoleacetic acid) is a measure of 5-HT turnover and has been used to assess neurochemical abnormalities in human psychiatric patients, and has potential in this regard for veterinary behavioral medicine. Neutraceuticals designed to augment 5-HT or 5-HT supplements may not engender the same response as to pharmacologic agents because 5-HT does not pass easily through the blood brain barrier (BBB), and instead requires the help of a transport protein. This transport protein is also used to move other amino acids across the BBB, and so - even if 5HT containing substances are absorbed unchanged from the GI tract, they may be excreted depending on the pharmacodynamics of the other amino acids present (6). Noradrenaline / norepinephrine (NE) The most prominent collection of noradrenergic neurons is found in the locus coeruleus of the grey matter of the pons and in the lateral tegmental nuclei. There is also a cluster in the medulla. NE has been postulated to affect (1) mood [NE decreases in depression and increases in mania], (2) functional reward systems, and (3) arousal. Dopamine The distribution of dopamine in the brain is non-uniform, but is more restrictive than that of NE. Dopaminergic nuclei are found primarily in: (1) the substantia nigra pars compacta which projects to the striatum and is largely concerned with coordinated movement; (2) the ventral tegmental area which projects to the frontal and cingulate cortex, nucleus acumbens, and other limbic structures; and (3) the arcuate nucleus of the hypothalamus which projects to the pituitary. A large proportion of the brain's dopamine is found in the corpus striatum, the part of the extrapyramidal system concerned with coordinated movement. Dopamine is metabolized by monamine oxidase (MAO) and catechol-O-methyl transferase (COMT) into dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA). HVA is used as a peripheral index of central dopamine turnover in humans, but this use has been little explored in veterinary medicine. All dopaminergic receptors are G-protein-coupled transmembrane receptors. The D1 receptors exhibit their post-synaptic inhibition in the limbic system and are affected in mood disorders and stereotypies. The D2, D3, and D4 receptors are all affected in mood disorders and stereotypies. Excess dopamine, as produced by dopamine releasing agents (amphetamines and dopamine agonists, like apomorphine) is associated with the development of stereotypies. Because of this - and because acepromazine is a neuroleptic agent that scrambles memory but does not prevent or treat anxiety - ACEPROMAZINE SHOULD NEVER BE USED AS A BEHAVIORAL MEDICATION OR AS A TREATMENT FOR STORM PHOBIAS. Gamma amino butyric acid (GABA) GABA, the inhibitory neurotransmitter found in short interneurons, is produced in large amounts only in the brain and serves as a neurotransmitter in ~30% of the synapses in the human CNS. The only long GABA-ergic tracts run to the cerebellum and striatum. GABA is formed from the excitatory amino acid (EEA) glutamate via glutamic acid decarboxylase (GAD), catalyzed by GABA-transaminase (GABA-T) and destroyed by transamination. There are two main groupings of GABA receptors - GABAA and GABAB. GABAA receptors, ligand-gated ion channels, mediate post-synaptic inhibition by increasing Cl- influx. Barbiturates and benzodiazepines are a potentiators of GABAA; however they do so by increasing the amount of time channels remain open - a relatively non-specific change. It is for this reason why these are NOT suitable behavioral medications, and why one is more likley to get a sedated, rather than a less anxious dog, when the dog is treated with phenobarbital for behavioral reasons. GABAB receptors are involved in the fine-tuning of inhibitory synaptic transmission: presynaptic GABAB receptors inhibit neurotransmitter release via high voltage activated Ca++ channels; postsynaptic GABAB receptors decrease neuronal excitability by activating inwardly rectifying K+ conductance underlying the late inhibitory post synaptic potential. GABA also has a variety of tropic effects on developing brain cells. During ontogeny GABAergic axons move through areas where other neurotransmitter phenotypes are being produced, and so may be related to later monoaminergic imbalances. The extent such ontogenic effects are relevant for behavioral conditions is currently unknown but bears investigating. EAAs (glutamate, aspartate, and, possibly, homocysteate) EEAs have a role as central neurotransmitters and are produced in abnormal levels in aggressive, impulse, and schizophrenic disorders. The main fast excitatory transmitters in the CNS are EEAs. Glutamate, widely and uniformly distributed in the CNS, is involved in carbohydrate and nitrogen metabolism. It is stored in synaptic vesicles and released by Ca2+ dependent exocytosis, so calcium channel blockers may affect conditions associated with increased glutamate. Both barbiturates and progesterone suppress excitatory responses to glutamate. Pre-synaptic barbiturates inhibit calcium uptake and decrease synaptosomal release of neurotransmitters, including GABA and glutamate. Roles for neuronal stimulation, synaptic plasticity, and receptor protein transcription and translation What makes TCAs and SSRIs special and why are they so useful for anxiety disorders? The key to the success of these drugs is that they utilize the same second messenger systems and transcription pathways that are used to develop cellular memory or to "learn" something. This pathway involves cAMP, cytosolic response element binding protein (CREB), brain derived neurotrophic factor (BDNF), NMDA receptors, protein tyrosine kinases (PTK) - particularly Src - which regulate activity of NMDA receptors and other ion channels and mediates the induction of LTP (long-term potentiation = synaptic plasticity) in the CA1 region of the hippocampus. There are two phases of TCA and SSRI treatment - short-term effects and long-term effects. Short-term effects result in a synaptic increase of the relevant monoamine associated with re-uptake inhibition. The somatodendric autoreceptor of the pre-synaptic neuron decreases the firing rate of that cell as a thermostatic response. Regardless, there is increased saturation of the post-synaptic receptors resulting in stimulation of the alpha-adrenergic coupled cAMP system. cAMP leads to an increase in PTK as the first step in the long-term effects. PTK translocates into the nucleus of the post-synaptic cell where it increases CREB, which has been postulated to be the post-receptor target for these drugs. Increases in CREB lead to increases in BDNF and tyrosine kinases (e.g., trkB) which then stimulate mRNA transcription of new receptor proteins. The altered conformation of the post-synaptic receptors renders serotonin stimulation and signal transduction more efficient. Knowledge of the molecular basis for the action of these drugs can aid in choosing treatment protocols. For example, the pre-synaptic somatodendritic autoreceptor is blocked by pindolol (a -adrenoreceptor antagonist) so augmentation of TCA and SSRI treatment with pindolol can accelerate treatment onset. Long-term treatment, particularly with the more specific TCAs (e.g., clomipramine) and SSRIs, employs the same pathway used in LTP to alter reception function and structure through transcriptional and translational alterations in receptor protein. This can be thought of as a form of in vivo "gene therapy" that works to augment neurotransmitter levels and production thereby making the neuron and the interactions between neurons more coordinated and efficient. In some patients short-term treatment appears to be sufficient to produce continued "normal" functioning of the neurotransmitter system. That there are some patients who require life-long treatment suggests that the effect of the drugs is reversible in some patients, further illustrating the underlying heterogeneity of the patient population considered to have the same diagnosis. Monitoring Monitoring of side-effects is critical for any practitioner dispensing behavioral medication. The first tier of this involves the same tests mandated in the pre-medication physical and laboratory evaluation. Age-related changes in hepatic mass, function, blood flow, plasma drug binding, et cetera cause a decrease in clearance of some TCAs, so it is prudent to monitor hepatic and renal enzymes annually in younger animals, biannually in older, and always as warranted by clinical signs. Adjustment in drug dosages may be necessary with age. It is generally preferable - but not necessarily required - to withdraw most patients from one class of drug before starting another. For most medications this is done so that one can be sure which medication is associated with any noted change in behavior. When changing between SSRIs and MAOIs a washout period is mandatory because of the potential for serotonin syndrom.......the recommended drug-free time in humans and dogs is two weeks (2 + half-lives: the general rule of thumb for withdrawal of any drug). Polypharmacy Oddly, because of the cytochrome systems that metabolize medication, it may be safer for the animal and more efficacious in terms improvement of the condition to combine medications. When medications are combined a knowledge of side effects and specific mechanisms of action is essential. That said, medications within related classes can usually be combined and such combination can allow a lower dose of each of the medications to be given. Medications of different classes can often be combined, if the potential side effects are compatible, and if the practitioner has a clear understanding of what conditions will or should respond to each medication. For example, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) can be combined with each other, and, if needed, with other medication within the class. For this to be done rationally, however, understanding potentiation of effect and side effects is essential. TCAs generally exert their largest effects on serotonin (5-HT) receptors, norepinephrine (NE) receptors, and some histaminic receptors (H). Additionally, they can have effects on some of the adrenergic receptors. The latter is important primarily when premedication for anesthesia is involved. SSRIs primarily affect 5-HT receptors, and most have an affinity for the 5-HT1a subtype receptor. Additionally, there are some weak effects on NE receptors. TCAs that are less specific (eg, amitiptyline) and SSRIs that are more specific (eg, fluoxetine) will be the easiest to combine since the overlap effects on the receptor will be less, while the generalized sensitization of the receptors in the class will be augmented. Combination treatment allows the clinician to use the lower end of the dosage for both compounds which minimizes side effects while maximizing efficacy. Furthermore, benzodiazepines can be used to blunt or prevent acute anxiety-related outbursts on an as needed basis in patients for whom daily treatment with a TCA or an SSRI is ongoing. Together, the combination of benzodiazepines and TCAs / SSRIs may hasten improvement and prevent acute anxiety-provoking stimuli from interfering with treatment of more regularly occurring anxieties. When stopping a drug, weaning is preferred to stopping abruptly (7). A model for how to do this is found below (7). Weaning minimizes potential central withdrawal signs, including those associated with serotonin dyscontinuation syndrome (8,9) and allows determination of the lowest dosage that is still effective. If patients are withdrawn fully, rather than weaned from medication, they may not have the same response to the medication that they had originally. Patients with dyscontinuation or cessation syndrome become moody and lethargic, but these effects usually pass within a week. If they do not, re-assessment of the wisdom of stopping medication is warranted. Medications that have the longest t 1/2 of intermediate metabolites (eg, fluoxetine) are less likely to cause problems when withdrawn quickly than are those with short half-lives or no functional intermediate metabolites (eg, paroxetine). However, SSRIs that have the greatest in vivo reuptake capabilities (eg, paroxetine) may be more at risk for involvement in serotonin syndrome. Long-term treatment may be the rule with many of these medications and conditions, but maintenance may be at a considerably lower level of drug than was prescribed at the outset. The only way the practitioner will discover if this is so is to withdraw the medication slowly. Because of these patterns, it is best NOT to withdraw animals from medication prior to anesthesia, but instead to adjust the pre-medication sedation so that fewer interactions - particularly of the adrenegic variety - can be expected. Finally, many animals appear to stop responding to medication. Staying the course may be the best decision in some of these cases because the CPY system is an inducible one, and multiple medication changes may just make the animal more - not less - refractory (10). Additionally, there is a huge range of genetic polymorphisms that determine how this system acts (11). These are all poorly understood in dogs because they have been so little investigated. However, given their importance in human psychiatry we'd be remiss if we didn't start to believe that such patterns may no be independent of disease state. Polypharmacy can be safe, rational, and cheap, and can save animals' lives. But this is an area that really requires an understanding of how these medications act. Fortunately, the functioning of these medications is easy to understand. Sample combinations (12) amitriptyline (TCA) + fluoxetine (SSRI) amitriptyline (TCA) + fluoxetine (SSRI) + alprazolam (BZ) amitriptyline (TCA) [anxiety] + alprazolam (BZ) [panic] fluoxetine (SSRI) [anxiety] + alprazolam (BZ) [panic] clomipramine (TCA - relatively specific) [anxiety] + alprazolam (BZ) [panic] clomipramine (TCA - relatively specific) [anxiety] + diazepam (BZ) [panic / phobias] - could be pretty sedating amitriptyline (TCA) [anxiety] + diazepam (BZ) [panic / phobias] - could be pretty sedating selegiline (MAO-I) (cognitive dysfunction) + diazepam (BZ) [panic / phobias] selegiline (MAO-I) (cognitive dysfunction) + alprazolam (BZ) [panic] paroxetine (SSRI) (social anxiety) + alprazolam (BZ) [panic / appetite stimulation in cats] Choosing specific drugs for the treatment of specific behavioral conditions Implicit in the recommendations for treatment are that the necessary and sufficient conditions for diagnosis are met (i.e., the practitioner is addressing a specific diagnosis, not a non-specific correlate or sign) and the relevant pharmacodynamics discussed above are understood and used in the diagnosis. Table 1 Half-lives of parent compounds and intermediate metabolites of target benzodiazepines in humans (6)
Table 2 Duration of action of parent compound, diazepam, and its intermediate metabolite, nordiazepam (N-desmethyl diazepam) in selected domestic animals (6)
Table 3 Relative effects of TCA parent compounds and intermediate metabolites on NE and 5-HT re-uptake (6)
* does not include the specific effect of the intermediate metabolite as a selective serotonin reuptake inhibitor (SSRI) Table 4 "Gestalt" of TCA and SSRI use based on t1/2 of parent compounds and active intermediate metabolites, relative effects on NE and 5-HT, and extrapolations from multi-center human studies (6)
Table 5 Algorithm for treatment length and weaning schedule (6) (1) Treat for as long as it takes to begin to assess effects: 7-10 days for relatively non-specific TCAs 3-5 weeks minimum for SSRIs and more specific TCAs PLUS (2) Treat until "well" and either have no signs associated with diagnosis or some low, consistent level: minimum of another 1-2 months PLUS (3) Treat for the amount of time it took you to attain the level discussed in (2) so that reliability of assessment is reasonably assured: minimum of another 1-2 months PLUS (4) Wean over the amount of time it took to get to (1) or more slowly. Remember, if receptor conformation reverts it may take 1+ months to notice the signs of this. While there are no acute side effects associated with sudden cessation of medication, a recidivistic event is a profound "side effect". Full-blown recidivistic events may not be responsive to re-initiated treatment with the same drug and, or the same dose: 7-10 days for relatively non-specific TCAs 3-5 weeks minimum for SSRIs and more specific TCAs TOTAL: Treat for a minimum of 4-6 months Table 6 a Selected psychopharmacological agents that may be useful in the treatment of feline behavioral diagnoses
Table 6 b Selected psychopharmacological agents that may be useful in the treatment of canine behavioral diagnoses
* veterinary label for some canine and feline conditions; label depends on country and species TOTAL: Treat for a minimum of 4-6 months References:
Anxiety-related conditions-Common signs and interventions Separation anxiety is one of the most common and most devastating behavioral conditions diagnosed world-wide in pet dogs. As is true for most behavioral conditions, the signs involved are non-specific. In the absence of treatment the outcome for affected dogs usually involves relinquishment to a humane society or shelter, abandonment, or euthanasia. Noise and thunderstorm phobias are among the most commonly recognized canine diagnoses associated with panicky or phobic responses, although no data exist on relative incidence of these problems. Based on the findings of a preliminary study finding a high concordance between dogs who exhibited signs of separation anxiety and those who met the criteria for noise or thunderstorm phobias, a detailed study (1) found an important correlation between these phobic responses and separation anxiety that suggests that the presence of one condition can affect the development and outcome of other related conditions. We now know: (1) that the development or expression of noise / thunderstorm phobias and separation anxiety are not independent, and the extent to which they co-vary may suggest differences in mechanisms for thresholds of anxiety - related disorders, and (2) that incidence and co-morbidity of both conditions may be underestimated or incompletely represented, even in a tertiary care behavioral practice setting, in the absence of a questionnaire or evaluation tool that systematically explores all responses to both related situations in all patients. This pattern appears to hold true for other behavioral conditions suggesting that the ontogeny of such conditions needs to be explored. In this case one can postulate, but not yet know that (1) reactions to noise may predispose dogs to other anxiety related conditions, and (2) the interaction of the 2 conditions may have time penetrance, and the longer an animal has been affected with one condition, the more at risk it might be either for a more complex form of the conditions (e.g., a greater number or intensity of signs). These questions are important if we are to understand the variability in behavioral conditions, and how best to treat them when first noticed. Finally, associations of any anxiety-related conditions with noise are important. Many human psychiatric patients experience aberrant noise reactivity, as do their unaffected, first degree relatives. Hence, understanding early responses that may contribute to overall reactivity and that may have heritable or genetic bases needs to become a research focus. In the example of separation anxiety and noise and thunderstorm / storm phobia the following definitions of the conditions were used to screen all patients for the relevant diagnoses (2). (1) Separation anxiety: Necessary condition - Physical or behavioral signs of distress exhibited by the animal only in the actual absence of, or lack of access to (virtual absence) the client; Sufficient condition - Consistent, intensive destruction, elimination, vocalization, or salivation exhibited only in the virtual or actual absence of the client; behaviors are most severe close to the separation, and many anxiety-related behaviors (autonomic hyperactivity, increased motor activity, and increased vigilance and scanning) may become apparent as the client exhibits behaviors associated with leaving. (2) Noise phobia: Necessary and sufficient conditions: Sudden and profound, non-graded, extreme response to noise, manifest as intense, active avoidance, escape, or anxiety behaviors associated with the activities of the sympathetic branch of the autonomic nervous system; behaviors can include catatonia or mania concomitant with decreased sensitivity to pain or social stimuli; repeated exposure results in an invariant pattern of response. (3) Thunderstorm / storm phobia: Necessary and sufficient conditions: Sudden and profound, non-graded, extreme response to thunderstorms or any aspect of them (e.g., wind, noise, lightening, changes in barometric pressure, rain, darkness, ozone level changes, et cetera) noise, manifest as intense, active avoidance, escape, or anxiety behaviors associated with the activities of the sympathetic branch of the autonomic nervous system; behaviors can include catatonia or mania concomitant with decreased sensitivity to pain or social stimuli; repeated exposure results in an invariant pattern of response. The use of such criteria allowed us to examine the distribution of non-specific signs independent of diagnosis. Non-specific signs may be uniquely important for assessing psycho-pathologically distinct groups (3). Improved understanding of the intensity, duration, age on onset, et cetera for specific symptoms will improve our description of the variable behavioral phenotypes that are associated with diagnostic sub-groups (4). The use of explicit definitional criteria are key to insuring that observed heterogeneity is not an artifact of careless classification. Elimination, destruction, and vocalization are the most obvious and hence the most commonly reported behaviors associated with separation anxiety. It's important to realize that clients complain about these behaviors because they are easy to recognize and are problems for the client. However, it is less easy to recognize dogs that are distressed when left, but exhibit less obvious signs like withdrawal and inactivity, salivation, soft whimpering (or frank barking and howling if there are no near neighbors), and pacing. These dogs are also painfully affected by separation anxiety, but their problems are not problems for the clients, so they seldom get help. With these dogs included, the population of dogs with separation anxiety, while unknown, is likely to be large indeed, and all dogs can benefit from treatment. A study of 141 dogs diagnosed with any of these conditions during a 12 month period produced the following patterns (1) .
It's interesting to not that client responses about the number of signs exhibited and the intensity / frequency of these signs were not independent of diagnosis or suites of diagnosis. Again, this finding supports the conclusion that the interaction of multiple pathological responses / diagnoses to situations associated with distress (noise phobia, separation anxiety, thunderstorm phobia) may either reflects an altered, dysfunctional, underlying neurochemical substrate, or is the result of one, and that the varying phenotypes displayed are the result of this dysfunction. The roles played by arousal and reactivity cannot be ignored if we are to understand dogs with anxiety-related conditions like separation anxiety, noise phobia, and thunderstorm phobia. Some dogs respond either more quickly to a stimulus, or react more intensely to a given stimulus that other dogs. At some level this "hyper-reactivity" is probably truly pathological and represents yet another phenotypical manifestation of some neurochemical variation associated with anxiety. If so, the more frequently the dog reacts to the anxiety provoking stimulus, the worse and more rapid the response. At some point any exposure can the result in a full-blown, non-graduated anxious reaction in which true panic may be involved. Accordingly, anticipation and early treatment is critical for these individuals, again supporting the concept that behavioral phenotype and underlying neurochemical response are linked in a dynamic way. Early intervention can only be accomplished by understanding the spectrum of signs exhibited in related conditions. If dogs follow the pattern common for co-morbid diagnoses as is found in humans, longer persistence of the signs and a less favorable overall outcome may one outcome of co-morbidity (10-11). In human medicine, childhood separation anxiety is seen as an important antecedent in adult panic disorder, and is prevalent as an undercurrent in the dreams of human panic disorder patients. This suggests that in humans, as in pets, separation anxiety can occur separate from panic disorder and other phobia-related conditions, but that when the two co-occur the interaction is an important factor in the assessment and treatment of either. If the phobic reactions to noise and storms are related to panic in dogs, such interactions are important. The conditional probability (see table) that a patient has separation anxiety, given that they have noise phobia is high (88%) and approximately the same as if they have thunderstorm phobia (87%). However, the probability that a patient has noise phobia is higher (74%) than the probability that they have thunderstorm phobia (61%), given that either have separation anxiety. These data, combined with the finding that the probability of having a noise phobia given a thunderstorm phobia is not equivalent to the converse (90% v. 76%), supports the hypothesis that neurochemical responses to noise are different from those to thunderstorms, if the behavioral phenotypes or endophenotypes are manifestations of repeated exposure and LTP. The property of unpredictability / uncertainty associated with thunderstorms may have a role in shaping the neurochemical and behavioral responses to anxiety provoking situations, suggesting future areas of exploration for understanding anxiety-related responses in dogs. Conditional probabilities for associations between SA, NP, and TP: P [SA / TP] = 0.8701 (87%) P [TP / SA] = 0.6147 (61%0 P [SA / NP] = 0.8804 (88%) P [NP / SA] = 0.7364 (74%) P [TP / NP] = 0.7609 (76%) P [NP / TP] = 0.8974 (90%) The data presented here demonstrate that when any noise reaction is involved the probability of having separation anxiety is greater than would otherwise be expected if the associations were random. This finding strongly suggest that adverse reactivity to noises, in general, may predispose a dog to separation anxiety, and that unless veterinarians carefully question clients about the pet's behavior both of these conditions could remain undiagnosed. The extent to which early fearful behaviors contribute to the development of separation anxiety is unknown. Overly fearful human youngsters are at risk for later emotional distress, including anxiety and depression, suggesting that such associations should be investigated in veterinary behavioral medicine. References:
K9 signals and their roles in understanding dogs that fight Normal dogs The uniting feature that connects all social vertebrates is the extent to which they signal non-verbally. Communication involving ritualized displays or graded signals is used to confirm or reject information received from others in social interactions, to indicate species, sex, and sexual receptivity, to signal about issues pertaining to status, and to otherwise negotiate all social interactions. As such, communication can involve such instantaneous behaviors as tactile and visual displays. These are relatively "short-distance" signals. Vocal communication is also instantaneous, but may reach over longer distances. Verbal communication is only one variety of vocal communication, and both of these may pale when the full story of olfactory communication is written. Certainly, olfactory and pheromonal signals provide information that can be assessed over distances and across time. When assessing any communicatory structure it is important to realize that signaling involves a set of rules that will be shaped by the evolutionary history of the species. The story of canine domestication is the story of work and work-related tasks. The story of feline domestication is the story of rodent and vector borne diseases and their prevention. These 2 divergent paths to domestic life-styles have been shaped by, and in turn have continued to shape factors like reproductive schedules, fecundity, age at first reproduction, age at sexual and social maturity, composition of family or group units, and social interactions within these units. To understand such behaviors it is critical to understand the component signals as they are used to communicate with conspecifics. The following tables provide an introduction to this topic. CANINE SIGNALS
A comment on early intervention and prevention of behavior problems: routine screening for behavioral problems: Most veterinarians obtain a routine history about physical complaints and concerns when they examine any dog or cat regardless of whether that pet is newly adopted or has been a beloved family member for a decade. We are all getting better about screening for geriatric health problems as we learn more about keeping pets happy and healthy for longer times. But the single biggest "health" problem faced by pet dogs and cats is still associated with behavioral pathologies or unmet behavioral expectations. Modern veterinary care should include routine screening about specific behavioral complaints in addition to routine questions that alert veterinarians to potential somatic medical problems. If we can ask "Any vomiting, diarrhea, changes in appetite?", we can also ask "Any inappropriate or undesirable chewing, any growling, any odd behaviors?". If we do this we accomplish the following goals: (1) We initiate a dialog with the clients about behavior. This lets them know that not only is behavior important, but it is central to good veterinary care. Clients will then feel comfortable asking their veterinarian about behavioral issues. Such dialog represents our best chance for learning of a client's behavioral concerns before these concerns threaten the pet's life. (2) We establish a baseline of the particular pet's behaviors. Such a behavioral profile will allow us learn "normal" for that pet so that we have a context in which to evaluate behavioral change or client complaints about behavior. This is exactly what we are doing when we recommend routine laboratory evaluation for healthy pets.........if we never knew when the pet last had a creatinine within the reference range it is difficult to know how long the creatinine has been elevated. Length of dysfunction - whether the dysfunction involves a "medical" or a "behavioral" complaint - can affect prognosis, and the extent to which this is true in behavioral medicine is profound. Basic questionnaires for dogs that can be completed at each visit are attached below (From: K.L. Overall, Clinical Behavioral Medicine for Small Animals, Mosby, St. Louis, 1997; revised for 2nd Edition, 12/00 & Overall, K.L. Manual of Clinical Behavioral Medicine for Small Animals, Elsevier, St. Louis, 2007). The questionnaire below is a survey questionnaire that can be used at any and all visits to check if the clients have any questions or complaints. You have to remember that the clients might not even know that they have questions or complaints because they do not know what "normal" is. Also, if anything, myths about breeds, behavior, nature, and nurture are far more insidious in the client community than in the veterinary community. This questionnaire, when used at each visit, together with the other more detailed and specific tools found in the references, above, will tell you if further information is necessary and hint at some of the underlying factors contributing to the problems. Finally, it's important to remember that the clients may not know what normal behavior is, or that they may be uncomfortable with a behavior, but not know how to ask if it is abnormal. These questionnaires will give clients the vocabulary and opportunity to discuss their pet's behaviors with their veterinarian in an efficient, consistent, and meaningful way. (1) Survey questionnaire about general canine behaviors:
Understanding dogs that fight To understand and help dogs that fight it is necessary to both understand their signaling in a larger context of overall pathological behavior, and how to utilize these signals to distinguish when animals are communicating and interacting normally from abnormally. Accordingly, we must give practitioners some guidance that can tell them where their patients might be on the continuum of normal, but scary to pathological, and possibly fatal. This is nowhere more important than for aggression between dogs because there is an almost uniform belief that some aggression can be 'normal' in dog-dog interactions. The inherent problem is whether the aggression label is misapplied to normal, tussling social behaviors. An approach that educates practitioners about behavioral patterns and sequelae can help here. Unfortunately, these goals are impossible to accomplish is we cleave to an outdated, unfortunate, and unsubstantiated terminology: that of the 'alpha' or 'dominant' dog. The modern and evolving understanding of complex social behaviors is going to require that we relinquish simplistic and damaging labels: the concept of a 'dominant' dog is not useful in these situations, and asking clients and practitioners to identify and support the 'dominant' dog can cause not just further morbidity, but mortality. An unpublished study of dozens of cases involving interdog aggression between household dogs (as contrasted with dogs with whom the participant(s) do not live) (1) found that most clients had been advised to support or reinforce the 'dominant' dog, and that when they did so, the aggression worsened. One could accordingly argue that the clients are any not correctly identifying the 'dominant' dog, but if a label is causing such difficulties, it may be time to just let it go. The issues of 'dominance' and social rank on group interactions comprise one of the oldest, most confusing, and hotly debated areas in the behavioral literature. It's important that we understand why this concept has caused problems in the practice of veterinary behavioral medicine. The existence of a hierarchy has been postulated to be a stress-reducing device (2); however, situations where hierarchies are most rigidly maintained are also ones where measures of stress are high (3). The traditional concepts are represented in the article under discussion: the animal who 'submits' - which is generally undefined - or gives way to another as a result of prior interactions is considered the 'subordinate' while the individual inducing such behavior is usually considered the 'dominant' animal in the pairing. 'Dominance' has been traditionally defined as individual's ability, generally under controlled situations, to maintain or regulate access to some resource (4-7). Given that the definition of 'dominance' can be further refined as a description of winning or losing staged contests over resources (8), and that a winning outcome needn't confer priority of access to those resources (8), we must accept that variable distributions of resources (e.g., access to attention, beds, resting sites, toys, food dishes, et cetera) will lead to variable hierarchal classifications. Concerns about such terminology primarily focus on 2 related issues: (1) the extent to which the labeling of an event, interaction, or pattern of interactions may interfere with our ability to truly understand behaviors and signals, in-context, and (2) the extent to which, if we subscribe to a hierarchical system, we are then tempted or constrained to force all interpretations of behaviors into that system. Such practices have encouraged humans to treat dogs inhumanely under the guise of being 'dominant' to them, and have likely resulted in the injury or death of many dogs because we have reinforced a truly pathological animal as 'dominant'. These concerns are not new: the potential to mislead was Rowell's primary concern when she published her ground-breaking study on the intricacies of baboon social interactions (9). In fact, when free-ranging baboon interactions were classified by behavioral types (e.g., friendly, approach-retreat), and then analyzed according to specific behaviors of the participants, no 'dominance' system was noted. A much more complex, elegant system of interactions that reflected relatedness, age, sex, social history, et cetera became apparent. Most social behaviors, when fully examined, are not characterized by agonistic encounters, but by fluid, context-specific deferential behaviors (10). Deference is not analogous to submission or subordination. Deference is about relative status that is freely given, not imposed. The animal to which most others defer is the animal that behaves most appropriately given the context, not the animal which must always be at the door first, or must eat first. In fact, a need to control regardless of context can be neither adaptive, nor normal. The role for deferential behaviors is suggested by authors who have looked extensively at social interactions when they discuss the variability in the behavior of high ranking animals. Accordingly, it may be easier to ask clients and practitioners to do 1 basic thing: correctly identify the animal in the interaction who is behaving most appropriately and protect and reinforce this animal. If clients and practitioners can watch videos of the dogs interacting in low-to-no risk circumstances, even without knowing what to call the behaviors, they will see differences. This is the first step in learning to better read feline and canine signaling. If they review enough interactions while emotionally removed from the situation (hence the use of video - real-time observations are notoriously unreliable), they will be able to recognize the animal whose behavior is most contextually appropriate. They will also able to identify the specific behaviors and signals of concern. Interactions are not an event - they are a process. A fight is a snap-shot viewed without the reference frame of the long movie that is the animals' lives together. In the absence of repeated snapshots, videos, or some other evaluation of social interaction over time, we can learn about variability in response and when it changes to abnormal by viewing a series of videos of dogs interacting with different outcomes. Clinicians can learn to read behaviors and assign probabilistic outcome to interactions using this type of approach. Clients need to know that their dogs will learn from their interactions with each other, and both 'combatants' may hone their aggressive skills. Attackers may become faster, and signal their intent less intensely with time, and victims may learn that they can minimize damage to themselves if they exhibit a pre-emptive attack. In such circumstances, it is easy to err in identifying the aggressor v the victim. The key is to able to identify when the behaviors are about learning normal social roles in changing social environments, and when they are about truly pathological behavior. Because learning works by altering neurochemistry (11), clients should understand that both early intervention designed to avert anxiety associated with underlying aggression and pharmacological intervention can help, but neither approach will be used appropriately until the clients can understand the signaling and interactions from the dogs' viewpoints (12). That said, some general guidelines that allow clients to deal with a range of potentially problematic interdog interactions from the relatively normal to the potentially fatal can be developed. The following example is from Step 3 of the Protocol for Interdog Aggression (13): 3. Choose an order in which to reinforce the dogs based on identifying which dog is behaving the most appropriately. Remember - reinforcement is not about rewarding the pushiest, most 'dominant' dog. It's about rewarding the dog who is most appropriate so that all the dogs get the message that obnoxious behaviors are not rewarded, but calm, non-threatening ones are. This type of reward-based reinforcement works because it mimics canine social systems and uses deferential behaviors to get attention and other 'currencies'. When you reinforce the most appropriate dog you feed that dog first, give him or her attention first, give them access to the yard first, et cetera. You can get hints about what will be most successful from the dogs' behaviors, as follows.
You are not imposing a 'rank' order on these dogs: instead, you are encouraging the normal types of social deference that would be exhibited by dogs under normal conditions. Unfortunately, myths about dog-dog relations are so ingrained that we have come to believe that dogs seize control and force others to wait for them. Nothing could be more wrong. By reinforcing an appropriately behaved dog you encourage the normal fluidity of the social system and can then reward the aggressive dog for not reacting. You can also more passively encourage the aggressor to understand that the victim has some status by allowing the victim sleep in a crate in your room, on a bed there, or on your bed (if you like this and the dog never growls at you while you are sleeping), while the other dog is banished to a room or crate outside your room. This has nothing to do with beds and 'spoiling' and everything to do with the fact that access to preferred spots or to attention is a currency for dogs. Regardless of how you decide to work with the dogs, each dog needs daily individual attention. The dog that is being reinforced should always get the attention first, in the presence of the other dog if this can be done quietly and without threats or overt aggression. If necessary, restrain the inappropriate dog using a harness. Finally, if you are walking the dogs as a group, make sure that if there is a dog that is "out in front", that dog is the one whose right to exist in an unmolested manner you are trying to reinforce. Under normal circumstances dogs should not need to care about who is in front of whom. If you are having these types of struggles on walks your canine household has issues that need to be addressed. If you are unsuccessful in gently requesting that the pushier dog steps back, consider some trial separations of the dogs to see if one dog blossoms when not harassed. If this happens, you need to work with the situation immediately. Remember that in anxiety-related conditions, like interdog aggression, many of the provocative behaviors are exhibited to gain information, and that part of the pathology may be that the dog is incapable of interpreting the response in all but the worse light for the victim. Also, abnormal dogs may misinterpret the behavior of a dog who pulls out in front of the others: to the normal dog, such behavior may just indicate that the dog is following a scent; to an abnormal dog the dog who pulled out in front may be seen as a deliberate threat. In this world view, treatment is about both understanding the neurochemical changes that occur with learning and repeated exposure, and about becoming humane. To do this, we must begin to see the world from the dog's point of view, which minimally requires that we let go of labels which may say more about us and our need, than they do about the behavior. The situation with interdog aggression demonstrate why we need to be more mindful of terminology, issues, and approaches which can inadvertently do more harm than good. References:
Rationale: The addition of psychotherapeutic agents to routine behavioral treatments, such as behavioral and environmental modification, has lead to better and faster treatment outcomes. In addition to facilitating better treatment of domestic animals and humans, psychopharmacological developments have permitted hypotheses about underlying mechanistic pathology to be tested. Mere treatment of non-specific behavioral complaints and signs is outdated (eg., treat barking by cutting the vocal cords) and has been replaced with an approach that includes ensuring that you meet the criteria for diagnosis, prior to treatment, followed by treatment that addresses the specific mechanism underlying the neurochemical contribution to the pathology (1). The use of medication should occur and is most effective as part of an integrated treatment program. There is no substitute for the hard work involved in behavior modification; however, some medications may be able to make it easier to implement the modification (2-4). Those seeking 'quick fix' solutions will doubtless be disappointed: inappropriate drug use will not alter the processes or environments that produced the behavior. While medication, alone, may render an animal globally less anxious, if the animal is still being provoked my social or physical environmental stimuli the benefit of treatment with medication will be minimized. It is partly this facile and inappropriate use of medication that has led many practitioners to falsely believe that medication does not work. Nothing could be further from the truth: the newer serotonin-affecting medications, protective neutraceutical, and enhanced dietary regimes have a huge potential improve life for troubled pets and their distressed people. In fact, rational drug use should now minimally be considered part of basic humane treatment of our patients. Adverse effects: The neurotransmitters affected by behavioral medications are acetylcholine, serotonin, norepinephrine (noradrenaline), dopamine, gamma amino butyric acid (GABA), and excitatory amino acids. Common adverse effects of psychotherapeutic drugs are usually caused by a blockage of the muscarinic acetylcholine receptors, which have diffuse connections throughout the brain. These 'common' side effects are actually quite rare and generally manifest themselves as transient changes in GI function or heart rate. If these side effect ARE NOT transient, clients need to understand that their pet may be experiencing a serious problem. For this reason, it is important to encourage clients to help monitor both their anima;'s response to the medication, and any side effects that they may have. Clients can easily learn to take pulse rates. Slight increases in pulse rate when treated with any medications affecting norepinephrine - as most the anti-anxiety agents do - are not worrisome. Huge, sustained increases are problematic. If clients know that their dog's resting heart rate is 65 bpm and with medication this changes to 150 bpm, they can immediately bring this change to their vet's attention. Likewise, if the increase is minor (65 to 75 bpm) they can relax and not worry. Educated clients will monitor their pets better, will be more willing to use medications and behavior mod appropriately, and will also be less likely to take the veterinarian's time needlessly. While many benzodiazepines (BZ) can be sedative, newer BZ have decreased sedative effects. Still, because dogs and cats, like humans, can experience a huge range of effects when given a BZ, clients should be encouraged to give any BZ when they can monitor the patient. This practice is extremely helpful in ensuring that we recognize animals with atypical or serious sedative responses so that we can find more appropriate medications with which to treat them. Most behavioral drugs are metabolized through renal and hepatic pathways so knowledge of baseline values is essential. That said, these medications can be used in compromised animals if adjustments are made and the animal is monitored behaviorally and biochemically. All psychotropic medications can interact with other medications. For example, use of most anti-anxiety agents will cause thyroidal values - whether or not supplementation is involved - for read falsely low. Many of serotnergic agents are thought to lower seizure thresholds and so are recommended with caution in patients treated with seizures. That said, there is now evidence in both the human and canine literature that anxiety may lower seizure thresholds and so treatment of the anxiety may allow the patient to successfully decrease the amount of seizure medication needed. Efficacy and mechanism of action: It's important for clients to understand that newer, more specific, more efficacious drugs have a relatively long lag time between initiation of treatment and apparent changes in the patient's behavior. This delay is due to the mechanism of action of the tricyclic antidepressants (TCAs) and the selective serotonin re-uptake inhibitors (SSRIs) which employ second messenger systems to alter transcription of receptor proteins. Serotonin (5-HT) receptors are all G-protein-coupled receptors. There are 14 identified classes of serotonin receptors. The 5-HT1 receptors are linked to the inhibition of adenylate cyclase and affect mood and behavior. Presynaptic 5-HT1A-receptors predominate in dorsal and median raphé nuclei; post-synaptic 5-HT1A-receptors predominant in limbic regions (hippocampus and septum) and some cortical layers. Activation of pre-synaptic receptors by agonists results in decreased firing of serotonergic neurons leading to transient suppression of 5-HT synthesis and decreased 5-HT release; activation of post-synaptic receptors decreases firing of post-synaptic cells. These are 'thermostatic' effects, not integrated outcomes of receptor activation. The overall effect depends on regulation of second messengers (cAMP, Ca2+, cGMP, IP3) and their effects on protein kinases which then alter neuronal metabolism and receptor protein transcription (5). The subclasses of 5-HT receptors vary in their affects. 5-HT1A receptors affect mood and behavior. 5-HT1D receptors affect cerebral blood vessels and appear to be involved in the development of migraine. These last two classes of receptor subtypes are the primary focus of many behavioral drugs. Urinary excretion of 5-HIAA (5-hydroxy indoleacetic acid) is a measure of 5-HT turnover and has been used to assess neurochemical abnormalities in human psychiatric patients, and has potential in this regard for veterinary behavioral medicine. Neutraceuticals designed to augment 5-HT or 5-HT supplements may not engender the same response as to pharmacologic agents because 5-HT does not pass easily through the blood brain barrier (BBB), and instead requires the help of a transport protein. This transport protein is also used to move other amino acids across the BBB, and so - even if 5HT containing substances are absorbed unchanged from the GI tract, they may be excreted depending on the pharmacodynamics of the other amino acids present (6). Noradrenaline / norepinephrine (NE): The most prominent collection of noradrenergic neurons is found in the locus coeruleus of the grey matter of the pons and in the lateral tegmental nuclei. There is also a cluster in the medulla. NE has been postulated to affect (1) mood [NE decreases in depression and increases in mania], (2) functional reward systems, and (3) arousal. Dopamine: The distribution of dopamine in the brain is non-uniform, but is more restrictive than that of NE. Dopaminergic nuclei are found primarily in: (1) the substantia nigra pars compacta which projects to the striatum and is largely concerned with coordinated movement; (2) the ventral tegmental area which projects to the frontal and cingulate cortex, nucleus acumbens, and other limbic structures; and (3) the arcuate nucleus of the hypothalamus which projects to the pituitary. A large proportion of the brain's dopamine is found in the corpus striatum, the part of the extrapyramidal system concerned with coordinated movement. Dopamine is metabolized by monamine oxidase (MAO) and catechol-O-methyl transferase (COMT) into dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA). HVA is used as a peripheral index of central dopamine turnover in humans, but this use has been little explored in veterinary medicine. All dopaminergic receptors are G-protein-coupled transmembrane receptors. The D1 receptors exhibit their post-synaptic inhibition in the limbic system and are affected in mood disorders and stereotypies. The D2, D3, and D4 receptors are all affected in mood disorders and stereotypies. Excess dopamine, as produced by dopamine releasing agents (amphetamines and dopamine agonists, like apomorphine) is associated with the development of stereotypies. Because of this - and because acepromazine is a neuroleptic agent that scrambles memory but does not prevent or treat anxiety - ACEPROMAZINE SHOULD NEVER BE USED AS A BEHAVIORAL MEDICATION OR AS A TREATMENT FOR STORM PHOBIAS. Gamma amino butyric acid (GABA): GABA, the inhibitory neurotransmitter found in short interneurons, is produced in large amounts only in the brain and serves as a neurotransmitter in ~30% of the synapses in the human CNS. The only long GABA-ergic tracts run to the cerebellum and striatum. GABA is formed from the excitatory amino acid (EEA) glutamate via glutamic acid decarboxylase (GAD), catalyzed by GABA-transaminase (GABA-T) and destroyed by transamination. There are two main groupings of GABA receptors - GABAA and GABAB. GABAA receptors, ligand-gated ion channels, mediate post-synaptic inhibition by increasing Cl- influx. Barbiturates and benzodiazepines are a potentiators of GABAA; however they do so by increasing the amount of time channels remain open - a relatively non-specific change. It is for this reason why these are NOT suitable behavioral medications, and why one is more likley to get a sedated, rather than a less anxious dog, when the dog is treated with phenobarbital for behavioral reasons. GABAB receptors are involved in the fine-tuning of inhibitory synaptic transmission: presynaptic GABAB receptors inhibit neurotransmitter release via high voltage activated Ca++ channels; postsynaptic GABAB receptors decrease neuronal excitability by activating inwardly rectifying K+ conductance underlying the late inhibitory post synaptic potential. GABA also has a variety of tropic effects on developing brain cells. During ontogeny GABAergic axons move through areas where other neurotransmitter phenotypes are being produced, and so may be related to later monoaminergic imbalances. The extent such ontogenic effects are relevant for behavioral conditions is currently unknown but bears investigating. EAAs (glutamate, aspartate, and, possibly, homocysteate): EEAs have a role as central neurotransmitters and are produced in abnormal levels in aggressive, impulse, and schizophrenic disorders. The main fast excitatory transmitters in the CNS are EEAs. Glutamate, widely and uniformly distributed in the CNS, is involved in carbohydrate and nitrogen metabolism. It is stored in synaptic vesicles and released by Ca2+ dependent exocytosis, so calcium channel blockers may affect conditions associated with increased glutamate. Both barbiturates and progesterone suppress excitatory responses to glutamate. Pre-synaptic barbiturates inhibit calcium uptake and decrease synaptosomal release of neurotransmitters, including GABA and glutamate. Roles for neuronal stimulation, synaptic plasticity, and receptor protein transcription and translation: What makes TCAs and SSRIs special and why are they so useful for anxiety disorders? The key to the success of these drugs is that they utilize the same second messenger systems and transcription pathways that are used to develop cellular memory or to "learn" something. This pathway involves cAMP, cytosolic response element binding protein (CREB), brain derived neurotrophic factor (BDNF), NMDA receptors, protein tyrosine kinases (PTK) - particularly Src - which regulate activity of NMDA receptors and other ion channels and mediates the induction of LTP (long-term potentiation = synaptic plasticity) in the CA1 region of the hippocampus. There are two phases of TCA and SSRI treatment: short-term effects and long-term effects. Short-term effects result in a synaptic increase of the relevant monoamine associated with re-uptake inhibition. The somatodendric autoreceptor of the pre-synaptic neuron decreases the firing rate of that cell as a thermostatic response. Regardless, there is increased saturation of the post-synaptic receptors resulting in stimulation of the -adrenergic coupled cAMP system. cAMP leads to an increase in PTK as the first step in the long-term effects. PTK translocates into the nucleus of the post-synaptic cell where it increases CREB, which has been postulated to be the post-receptor target for these drugs. Increases in CREB lead to increases in BDNF and tyrosine kinases (e.g., trkB) which then stimulate mRNA transcription of new receptor proteins. The altered conformation of the post-synaptic receptors renders serotonin stimulation and signal transduction more efficient. Knowledge of the molecular basis for the action of these drugs can aid in choosing treatment protocols. For example, the pre-synaptic somatodendritic autoreceptor is blocked by pindolol (a -adrenoreceptor antagonist) so augmentation of TCA and SSRI treatment with pindolol can accelerate treatment onset. Long-term treatment, particularly with the more specific TCAs (e.g., clomipramine) and SSRIs, employs the same pathway used in LTP to alter reception function and structure through transcriptional and translational alterations in receptor protein. This can be thought of as a form of in vivo "gene therapy" that works to augment neurotransmitter levels and production thereby making the neuron and the interactions between neurons more coordinated and efficient. In some patients short-term treatment appears to be sufficient to produce continued "normal" functioning of the neurotransmitter system. That there are some patients who require life-long treatment suggests that the effect of the drugs is reversible in some patients, further illustrating the underlying heterogeneity of the patient population considered to have the same diagnosis. Monitoring: Monitoring of side-effects is critical for any practitioner dispensing behavioral medication. The first tier of this involves the same tests mandated in the pre-medication physical and laboratory evaluation. Age-related changes in hepatic mass, function, blood flow, plasma drug binding, et cetera cause a decrease in clearance of some TCAs, so it is prudent to monitor hepatic and renal enzymes annually in younger animals, biannually in older, and always as warranted by clinical signs. Adjustment in drug dosages may be necessary with age. It is generally preferable - but not necessarily required - to withdraw most patients from one class of drug before starting another. For most medications this is done so that one can be sure which medication is associated with any noted change in behavior. When changing between SSRIs and MAOIs a washout period is mandatory because of the potential for serotonin syndrom.......the recommended drug-free time in humans and dogs is two weeks (2 + half-lives: the general rule of thumb for withdrawal of any drug). Polypharmacy: Oddly, because of the cytochrome systems that metabolize medication, it may be safer for the animal and more efficacious in terms improvement of the condition to combine medications. When medications are combined a knowledge of side effects and specific mechanisms of action is essential. That said, medications within related classes can usually be combined and such combination can allow a lower dose of each of the medications to be given. Medications of different classes can often be combined, if the potential side effects are compatible, and if the practitioner has a clear understanding of what conditions will or should respond to each medication. For example, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) can be combined with each other, and, if needed, with other medication within the class. For this to be done rationally, however, understanding potentiation of effect and side effects is essential. TCAs generally exert their largest effects on serotonin (5-HT) receptors, norepinephrine (NE) receptors, and some histaminic receptors (H). Additionally, they can have effects on some of the adrenergic receptors. The latter is important primarily when premedication for anesthesia is involved. SSRIs primarily affect 5-HT receptors, and most have an affinity for the 5-HT1a subtype receptor. Additionally, there are some weak effects on NE receptors. TCAs that are less specific (eg, amitiptyline) and SSRIs that are more specific (eg, fluoxetine) will be the easiest to combine since the overlap effects on the receptor will be less, while the generalized sensitization of the receptors in the class will be augmented. Combination treatment allows the clinician to use the lower end of the dosage for both compounds which minimizes side effects while maximizing efficacy. Furthermore, benzodiazepines can be used to blunt or prevent acute anxiety-related outbursts on an as needed basis in patients for whom daily treatment with a TCA or an SSRI is ongoing. Together, the combination of benzodiazepines and TCAs / SSRIs may hasten improvement and prevent acute anxiety-provoking stimuli from interfering with treatment of more regularly occurring anxieties. When stopping a drug, weaning is preferred to stopping abruptly (7). A model for how to do this is found below (7). Weaning minimizes potential central withdrawal signs, including those associated with serotonin dyscontinuation syndrome (8,9) and allows determination of the lowest dosage that is still effective. If patients are withdrawn fully, rather than weaned from medication, they may not have the same response to the medication that they had originally. Patients with dyscontinuation or cessation syndrome become moody and lethargic, but these effects usually pass within a week. If they do not, re-assessment of the wisdom of stopping medication is warranted. Medications that have the longest t 1/2 of intermediate metabolites (eg, fluoxetine) are less likely to cause problems when withdrawn quickly than are those with short half-lives or no functional intermediate metabolites (eg, paroxetine). However, SSRIs that have the greatest in vivo reuptake capabilities (eg, paroxetine) may be more at risk for involvement in serotonin syndrome. Long-term treatment may be the rule with many of these medications and conditions, but maintenance may be at a considerably lower level of drug than was prescribed at the outset. The only way the practitioner will discover if this is so is to withdraw the medication slowly. Because of these patterns, it is best NOT to withdraw animals from medication prior to anesthesia, but instead to adjust the pre-medication sedation so that fewer interactions - particularly of the adrenegic variety - can be expected. Finally, many animals appear to stop responding to medication. Staying the course may be the best decision in some of these cases because the CPY system is an inducible one, and multiple medication changes may just make the animal more - not less - refractory (10). Additionally, there is a huge range of genetic polymorphisms that determine how this system acts (11). These are all poorly understood in dogs because they have been so little investigated. However, given their importance in human psychiatry we'd be remiss if we didn't start to believe that such patterns may no be independent of disease state. Polypharmacy can be safe, rational, and cheap, and can save animals' lives. But this is an area that really requires an understanding of how these medications act. Fortunately, the functioning of these medications is easy to understand. Sample combinations (12) : amitriptyline (TCA) + fluoxetine (SSRI) amitriptyline (TCA) + fluoxetine (SSRI) + alprazolam (BZ) amitriptyline (TCA) [anxiety] + alprazolam (BZ) [panic] fluoxetine (SSRI) [anxiety] + alprazolam (BZ) [panic] clomipramine (TCA - relatively specific) [anxiety] + alprazolam (BZ) [panic] clomipramine (TCA - relatively specific) [anxiety] + diazepam (BZ) [panic / phobias] - could be pretty sedating amitriptyline (TCA) [anxiety] + diazepam (BZ) [panic / phobias] - could be pretty sedating selegiline (MAO-I) (cognitive dysfunction) + diazepam (BZ) [panic / phobias] selegiline (MAO-I) (cognitive dysfunction) + alprazolam (BZ) [panic] paroxetine (SSRI) (social anxiety) + alprazolam (BZ) [panic / appetite stimulation in cats] "Gestalt" of TCA and SSRI use based on t1/2 of parent compounds and active intermediate metabolites, relative effects on NE and 5-HT, and extrapolations from multi-center human studies (7)
Algorithm for treatment length and weaning schedule (7) (1) Treat for as long as it takes to begin to assess effects: 7-10 days for relatively non-specific TCAs 3-5 weeks minimum for SSRIs and more specific TCAs PLUS (2) Treat until "well" and either have no signs associated with diagnosis or some low, consistent level: minimum of another 1-2 months PLUS (3) Treat for the amount of time it took you to attain the level discussed in (2) so that reliability of assessment is reasonably assured: minimum of another 1-2 months PLUS (4) Wean over the amount of time it took to get to (1) or more slowly. Remember, if receptor conformation reverts it may take 1+ months to notice the signs of this. While there are no acute side effects associated with sudden cessation of medication, a recidivistic event is a profound "side effect". Full-blown recidivistic events may not be responsive to re-initiated treatment with the same drug and, or the same dose: 7-10 days for relatively non-specific TCAs 3-5 weeks minimum for SSRIs and more specific TCAs TOTAL: Treat for a minimum of 4-6 months References:
Separation anxiety is one of the most common and most devastating behavioral conditions diagnosed world-wide in pet dogs. As is true for most behavioral conditions, the signs associated with In the absence of treatment the outcome for affected dogs usually involves relinquishment to a humane society or shelter, abandonment, or euthanasia. Noise and thunderstorm phobias are among the most commonly recognized canine diagnoses associated with panicky or phobic responses, although no data exist on relative incidence of these problems. Based on the findings of a preliminary study finding a high concordance between dogs who exhibited signs of separation anxiety and those who met the criteria for noise or thunderstorm phobias, a detailed study (1) found an important correlation between these phobic responses and separation anxiety that suggests that the presence of one condition can affect the development and outcome of other related conditions. We now know: (1) that the development or expression of noise / thunderstorm phobias and separation anxiety are not independent, and the extent to which they co-vary may suggest differences in mechanisms for thresholds of anxiety - related disorders, and (2) that incidence and co-morbidity of both conditions may be underestimated or incompletely represented, even in a tertiary care behavioral practice setting, in the absence of a questionnaire or evaluation tool that systematically explores all responses to both related situations in all patients. This pattern appears to hold true for other behavioral conditions suggesting that the ontogeny of such conditions needs to be explored. In this case one can postulate, but not yet know that (1) reactions to noise may predispose dogs to other anxiety related conditions, and (2) the interaction of the 2 conditions may have time penetrance, and the longer an animal has been affected with one condition, the more at risk it might be either for a more complex form of the conditions (e.g., a greater number or intensity of signs). These questions are important if we are to understand the variability in behavioral conditions, and how best to treat them when first noticed. Finally, associations of any anxiety-related conditions with noise are important. Many human psychiatric patients experience aberrant noise reactivity, as do their unaffected, first degree relatives. Hence, understanding early responses that may contribute to overall reactivity and that may have heritable or genetic bases needs to become a research focus. In the example of separation anxiety and noise and thunderstorm / storm phobia the following definitions of the conditions were used to screen all patients for the relevant diagnoses (2). (1) Separation anxiety: Necessary condition - Physical or behavioral signs of distress exhibited by the animal only in the actual absence of, or lack of access to (virtual absence) the client; Sufficient condition - Consistent, intensive destruction, elimination, vocalization, or salivation exhibited only in the virtual or actual absence of the client; behaviors are most severe close to the separation, and many anxiety-related behaviors (autonomic hyperactivity, increased motor activity, and increased vigilance and scanning) may become apparent as the client exhibits behaviors associated with leaving. (2) Noise phobia: Necessary and sufficient conditions: Sudden and profound, non-graded, extreme response to noise, manifest as intense, active avoidance, escape, or anxiety behaviors associated with the activities of the sympathetic branch of the autonomic nervous system; behaviors can include catatonia or mania concomitant with decreased sensitivity to pain or social stimuli; repeated exposure results in an invariant pattern of response. (3) Thunderstorm / storm phobia: Necessary and sufficient conditions: Sudden and profound, non-graded, extreme response to thunderstorms or any aspect of them (e.g., wind, noise, lightening, changes in barometric pressure, rain, darkness, ozone level changes, et cetera) noise, manifest as intense, active avoidance, escape, or anxiety behaviors associated with the activities of the sympathetic branch of the autonomic nervous system; behaviors can include catatonia or mania concomitant with decreased sensitivity to pain or social stimuli; repeated exposure results in an invariant pattern of response. The use of such criteria allowed us to examine the distribution of non-specific signs independent of diagnosis. Non-specific signs may be uniquely important for assessing psycho-pathologically distinct groups (3). Improved understanding of the intensity, duration, age on onset, et cetera for specific symptoms will improve our description of the variable behavioral phenotypes that are associated with diagnostic sub-groups (4). The use of explicit definitional criteria are key to insuring that observed heterogeneity is not an artifact of careless classification. Elimination, destruction, and vocalization are the most obvious and hence the most commonly reported behaviors associated with separation anxiety. It's important to realize that clients complain about these behaviors because they are easy to recognize and are problems for the client. However, it is less easy to recognize dogs that are distressed when left, but exhibit less obvious signs like withdrawal and inactivity, salivation, soft whimpering (or frank barking and howling if there are no near neighbors), and pacing. These dogs are also painfully affected by separation anxiety, but their problems are not problems for the clients, so they seldom get help. With these dogs included, the population of dogs with separation anxiety, while unknown, is likely to be large indeed, and all dogs can benefit from treatment. A study of 141 dogs diagnosed with any of these conditions during a 12 month period produced the following patterns (1) .
It's interesting to not that client responses about the number of signs exhibited and the intensity / frequency of these signs were not independent of diagnosis or suites of diagnosis. Again, this finding supports the conclusion that the interaction of multiple pathological responses / diagnoses to situations associated with distress (noise phobia, separation anxiety, thunderstorm phobia) may either reflects an altered, dysfunctional, underlying neurochemical substrate, or is the result of one, and that the varying phenotypes displayed are the result of this dysfunction. The roles played by arousal and reactivity cannot be ignored if we are to understand dogs with anxiety-related conditions like separation anxiety, noise phobia, and thunderstorm phobia. Some dogs respond either more quickly to a stimulus, or react more intensely to a given stimulus that other dogs. At some level this "hyper-reactivity" is probably truly pathological and represents yet another phenotypical manifestation of some neurochemical variation associated with anxiety. If so, the more frequently the dog reacts to the anxiety provoking stimulus, the worse and more rapid the response. At some point any exposure can the result in a full-blown, non-graduated anxious reaction in which true panic may be involved. Accordingly, anticipation and early treatment is critical for these individuals, again supporting the concept that behavioral phenotype and underlying neurochemical response are linked in a dynamic way. Early intervention can only be accomplished by understanding the spectrum of signs exhibited in related conditions. If dogs follow the pattern common for co-morbid diagnoses as is found in humans, longer persistence of the signs and a less favorable overall outcome may one outcome of co-morbidity (10-11). In human medicine, childhood separation anxiety is seen as an important antecedent in adult panic disorder, and is prevalent as an undercurrent in the dreams of human panic disorder patients. This suggests that in humans, as in pets, separation anxiety can occur separate from panic disorder and other phobia-related conditions, but that when the two co-occur the interaction is an important factor in the assessment and treatment of either. If the phobic reactions to noise and storms are related to panic in dogs, such interactions are important. The conditional probability (see table) that a patient has separation anxiety, given that they have noise phobia is high (88%) and approximately the same as if they have thunderstorm phobia (87%). However, the probability that a patient has noise phobia is higher (74%) than the probability that they have thunderstorm phobia (61%), given that either have separation anxiety. These data, combined with the finding that the probability of having a noise phobia given a thunderstorm phobia is not equivalent to the converse (90% v. 76%), supports the hypothesis that neurochemical responses to noise are different from those to thunderstorms, if the behavioral phenotypes or endophenotypes are manifestations of repeated exposure and LTP. The property of unpredictability / uncertainty associated with thunderstorms may have a role in shaping the neurochemical and behavioral responses to anxiety provoking situations, suggesting future areas of exploration for understanding anxiety-related responses in dogs. Conditional probabilities for associations between SA, NP, and TP: P [SA / TP] = 0.8701 (87%) P [TP / SA] = 0.6147 (61%0 P [SA / NP] = 0.8804 (88%) P [NP / SA] = 0.7364 (74%) P [TP / NP] = 0.7609 (76%) P [NP / TP] = 0.8974 (90%) The data presented here demonstrate that when any noise reaction is involved the probability of having separation anxiety is greater than would otherwise be expected if the associations were random. This finding strongly suggest that adverse reactivity to noises, in general, may predispose a dog to separation anxiety, and that unless veterinarians carefully question clients about the pet's behavior both of these conditions could remain undiagnosed. The extent to which early fearful behaviors contribute to the development of separation anxiety is unknown. Overly fearful human youngsters are at risk for later emotional distress, including anxiety and depression, suggesting that such associations should be investigated in veterinary behavioral medicine. References:
Epidemiology of cat bites: Problem aggression is second only to elimination disorders in commonness of complaints about cat behavior. Given the multifaceted role played by scent in feline social systems, this should not be surprising. Unfortunately, the extent to which the interaction between feline aggression and elimination disorders is involved in tough problems is under-appreciated. Feline aggression is emerging as a common and worrisome problem, especially when viewed with regard to its potential to cause serious illness in people. Cat scratch disease: 22,000 cases - 1.8-10 cases / 100,000 people - of cat scratch disease are reported each year in the U.S.; 2,200 people are hospitalized, annually. The presumptive agent in cat scratch disease (CSD) is the rickettsial organism Bartonella (formerly Rochalimaea) hensalae, and a contributory role has been postulated for the bacteria Afipia felis. 38/45 patients with CSD had titers of >/= 1:64 for Bartonella hensalae. CSD is most commonly seen in the late summer and fall and coincides with seasonality in births of kittens (spring) and the entry of these kittens into the house in the winter. Fleas infestations may be associated with a higher incidence of the CSD and most patients have at least 1 kitten that has fleas. Patients with CSD are more likely to have a kitten less than or a year of age, or to have been scratched by a kitten than are non-patients. While patients in kitten-owning households are more likely to have been scratched or bitten than patients in non-kitten owning households, there appears to be no association with patients' cats and those of controls with regard to indoor / outdoor status, litter box use, and hunting behaviors. Cats transmitting CSD appear healthy although they have active B. hensalae infections that last months. People with CSD tend to have localized skin lesions that are followed by regional lymph node involvement 3 weeks post exposure. Lymph nodes remain enlarged for several months. Systematic illness is rare, but fever, headache, splenomegaly, and malaise are common. These are usually self-resolving; however, arthritis, neuroretinitis, pleurisy, pneumonia, osteolytic lesions, granulomatous hepatitis, and encephalitis, with coma and seizure, can be an unusual sequela. Individuals with AIDS or those immunosuppressed for other reasons are at risk for more severe disease, including bacillary angiomatosis. In addition to being a human health hazard, CSD is costly: the cost of treatment for ambulatory patients averages $5.2 million per year, and the cost of treatment for hospitalized patients exceeds $6.9 million per year, in 1990s USD. Cat scratch disease is an occupational hazard for those working in veterinary medicine. When cats are fearful or distressed, they try to escape and withdraw. As a precursor to withdrawal, or as a means to make withdrawal possible, cats will bit and scratch. Understanding how to better handle cats in veterinary settings and how to teach clients to better accustom cats to veterinary visits should reduce the number of injuries to humans. Aggressive behaviors: Survey studies indicate that, over their lifetime, 80% of cats hiss at each other, 85% swat at each other, 70% fight with each other occasionally, 25% hiss / growl at people and 60% of them scratch or bite people occasionally. 53.6% of the cats in this study exhibited hissing sometimes (1 time per month) or frequently (1+ times per week), 63.1% exhibited swatting sometimes or frequently, and 44.5% exhibiting fighting sometimes or frequently. Statistical examination of data collected by Borchelt and Voith (1987) indicate that cats are more often aggressive to other cats than people in situations involving defensive and territorial aggression (p<0.05; Gadj=32.627 and 11.442, respectively), but are more often aggressive to people when compared with cats in circumstances involving play aggression (p<0.05; Gadj=25.091). Their study did not evaluate a baseline of normal behaviors (perhaps cats are not involved in play aggression often with cats because they are corrected by the other cats sufficiently early in the sequence of play to avoid frank aggression), but suggests situations in which people might be at risk. The aggressive behavior of the cats may not be manifest the same way towards all people. There are few actual data on cat bites, and those that have been published generally provide no statistical examination of the data, but if authors publish their data, others can do I as have done, and provide the analysis. Careful examination of data published by Borchelt and Voith (1987) indicates that for cats that are deemed "frequently" aggressive, there is no difference between the frequency of growling or hissing that is directed towards strangers compared with that directed towards family members (ns; Gadj=0.209), but that family members are more frequently subjected to swatting, scratching and biting without breaking the skin, and bites that break the skin (p<0.05; Gadj=21.197,30.014, and 9.554, respectively). Closer statistical investigation reveals that family members are more frequently victimized than are strangers by cats that break the skin, only by cats that have inflicted 3,4, or more than 8 bites (p<0.05; Gadj=3.874, 4.179, 22.311, respectively). Categories of feline aggression - associations with human / cat aggression: It's important to remember that some of the circumstances in which humans will be injured by cats may involve "normal" aggressive behavior on the part of the cat. Cats who protect their kittens when there is really a threat are not showing manifestations of a diagnosis of maternal aggression. Likewise, cats who are afraid of a real threat are behaving normally and appropriately, rather than demonstrating manifestations of fearful aggression. Seen within this context, much of the aggression demonstrated at veterinary practices is normal aggression associated with fear. Accordingly, we can address this by either learning how to anticipate the problem, and lesson the result, and, or by preventing it. The easiest way to prevent such aggression is to acclimate the cat to the situation. Cats respond most plastically to novel stimuli between 5 and 9 weeks of age, and their ability to remain flexible in response to novel stimuli decreases greatly by 14 weeks of age, if they have not been previously exposed to novel situations. Although the data have not been completely collected, early exposure to a variety of stimuli that are not terrifying may be necessary for the cat to learn to learn. In other words, if the cat is "protected" from the world, they may have decreased plasticity in their responses to changes in social and environmental stimuli later in life. We can use this information to benefit the cat's overall "wellness" and mental health: simply, any client with a kitten should take advantage of the cat's natural curiosity and energy and stimulate the kitten to explore and interact with as many environments as possible. First, clients should fit their kittens with harness and light-weight lead and encourage the cat to go for walks outside of the house or apartment. If the cat is slightly nervous, he or she can just sit on the client's lap and be an observer until the cat decides to venture forth. Even if the clients have a back yard, it is safer, more humane, and more considerate for neighbors if the cat is kept on a lead or a trolley. For these to be safe, clients need to supervise the cat. If clients wish to give their cat the experience of the outdoors without supervising them, outdoor habitats can now be built with very little effort or custom made to encircle trees, branches, decks, and windows. Second, clients should be encouraged to carry and use treats for cats as they do for dogs. Most kittens will readily work for small shrimp, dried liver or bacon, or a dab of some of the salty, fermented spreads (e.g., Marmite, Veg-e-mite). The key is convincing the clients that their little balls of fluff are intelligent, cognitive, curious beings who can be trained to work with the client. If clients would interact with their cats in this manner both of their cognitive lives would be enriched. Third, clients should be encouraged to take the cat with them - temperature permitting - in the car whenever they can. Cats can be restrained in car harnesses, in an open crate, or using pet gates. Fourth, clients should be encouraged to take their cat visiting to the vet's multiple times during the cat's first year of life. If the cat visits the vet and all that happens is that the cat is petted, fussed over, played with, and given treats, the cat will learn that this is good place to visit. Routine exams will then become easier, if the vet continues buying into and encouraging the concept of positive rewards and interactions. For example, if the cat is not worried about getting into the carrier and going to the vets, then when he gets there he might be far more interested in the food treat that is smeared on the exam table than he is in fighting the vet. Getting vets to buy into the idea of using toys and treats at every visit is not a trivial problem. Most vets are concerned about their tightly booked appointments and the time / money conundrum. However, most of us fail to accurately account for all the time we struggle with patients and clients, all the times we need more hands than we have to restrain an animal, and for the real cost to us and the patient - in both physical and emotional terms - of such struggles. Were we to do an accurate accounting, we would be investing in any strategy that lowers our frustration time and our patients' stress levels. An easy way to get vets to start working with cats differently is to hold kitten classes. While many practices hold puppy classes, few practices in the US hold kitten classes (but many in Australia, do: see Training Your Cat by Kersti Seksel, Hyland House, Australia, 2001). These are ideal for kittens 8-13 weeks of age, and if conducted in 2 sessions allows the veterinary staff to cover all relevant preventative behavioral and medical topics, and also permits adequate time to teach clients how to play with cats, to encourage clients to watch normal cat behavior, and to teach the cats to sit, stay, come, do a trick, and to walk on lead and harness. Tables 1 and 2 contain a summary of information to discuss at the first appointments, or - preferably - in kitten classes. If it is impossible to cover all of this information during the first examination, a series of short-examinations, arranged as a package at one price, or a long first puppy or kitten visit (2 hours can be a realistic estimate) arranged as part of a package deal with all vaccinations can be options. Videos, client handouts, and support staff participation are invaluable. If the puppy or kitten is going to undergoing a series of three vaccinations, the information can be outlined at the first visit and a schedule of topics to cover at that and subsequent visits developed. There are many variants on this approach and ALL are somewhat labor intensive; however, that labor pays off. Clients want information and will pay for it and treatment later if they received it first. Also, pets that are killed because of later behavioral problems do not generate income and do not contribute to an attitude and bond that encourages the generation of income. What veterinarians should NOT do on the first visit, is rush the pup or kitten through in 5 minutes (because it is generally healthy) and quickly (and scarily - to the pet) vaccinate it. First visits may not even involve a vaccination - that activity may be better executed the next day (when it could be done quickly after a temperature check if the first visit included a thorough physical examination). The first visit should involve acquaintance with the staff, play, fuss, treats, a physical examination, and possibly, a vaccination sneaked in at the end of play. Encourage clients to return between appointments to just visit - this is great for the puppy or kitten and them. Of course they will ask your staff questions, but they can also be told up front, when invited to drop in, that if the staff is too busy for the visit they will say so. These activities are outlined in the checklists in Tables 1 and 2. Clients should practice these activities often, whether the pet "needs" them or not. Obviously, toe nails should not be clipped or filed unless needed, but the client can manipulate the kitten's toes and hold them in the way they would when they clip them. This will make the actual activity easier. Repeated exposure of the new pet to these activities will help the client in two respects: (1) they will help render then pet more tractable and less fearful of manipulation, and (2) they will familiarize the client with "normal" so that they can report deviations from this to you. When considering whether a cat's aggression is contextually appropriate or 'normal', it is important to bear in mind the evolutionary derivation of domestic cats, especially since this differs dramatically from that of dogs. Feline social systems differ from those of dogs in the extent to which solitary versus social daily activities are prevalent. Cats are primarily solitary hunters, ingesting prey that is smaller than they are, whereas most wild canids work in groups to obtain prey larger than themselves. These forces will act to shape social relationships within groups. Cats can hunt sufficiently for one meal alone, while dogs use this only as a back-up foraging strategy. Dogs are more aligned with the "binge and gorge" eating style than are cats. Because cats don't rely on running down prey and exhausting them before the group moves in to attack, stealth is much more important to cats than it is to dogs, and it may be associated with the cat's normal tendency to hide when stressed or distressed. Finally, it's really important to remember that the history of cats and humans is the history of disease control: cats were attracted to rodents who are always attracted to human garbage. Cats killed the rodents that carried diseases or vectors of disease. Consequently, there has been little artificial selection by humans on how cats behave. In fact, selection for how they look is fairly recent and only taken place intensely in the past 200 years. Dogs were selected because of their shared behaviors with humans to help humans in tasks in which both species engaged. Hence, breeds in dogs have their roots in the jobs the dogs did - not what they looked like. As a consequence of their evolutionary system, matrilineal social system, and skewed sex ratios for mating in free-ranging domestic casts, Most normal aggression between cats appears to occur in contexts involving territory and social rank which are complexly interrelated. It is not surprising that the types of inappropriate aggression witnessed by owners differ from those that we perceive in dogs, and that they are understandable given the evolutionary context of feline social systems and the developmental context of sensitive periods. Attention has been paid to the extent to which feline aggression is covert, rather than overt and defensive, rather than offensive (Table 3). These can be useful distinctions in understanding and intervening in the interactions between cats and other individuals involved in the aggressive circumstances. Clients must learn to read the signs of these behaviors to correctly interpret the ongoing interaction and to help us to treat the problem appropriately. Offensive aggression generally involves components that decrease the distance between the individuals. These behaviors can include approach (as a threat with subsequent flight of the other individual) and attack. Regardless, the aggressor controls the interaction through the use of threat or the escalation of violence. Defensive aggression involves passive behaviors designed to encourage avoidance and withdrawal. This serves to remove the stimulus for further aggression (Young, 1988). Spraying can act as a defensively aggressive behavior when it serves this purpose. Client often have trouble recognizing aggression within their feline household because they are only aware of overt forms of aggression. It will help them if you emphasize that cats are not small dogs: the most common form of aggression in cats is subtle, covert aggression that involves posturing on the part of the aggressor and deference on the part of the recipient of the aggression. Assertions that cats are not social have interfered with our ability to understand both these types of aggressions when they occur between cats and when they are directed by the cat to people (assertion or status-related aggression). Cats generally exhibit overt aggression when they perceive each other as equal rivals and neither cat defers to the other. This situation is more common in crowded situations like laboratory colonies, households with too many cats, or urban, stray groupings. Covert aggression is more likely to occur if cats know each other well, and if all cats involved either agree that they do not see each other as equals, or if some cat is not sufficiently confident to overtly challenge another cat. Spraying and non-spraying marking can play a role in both of these circumstances. Categorization of feline aggression is similar to that of canine aggression; differences in the manifestation of the aggressions may be attributable to differences in mating behaviors and differences in social hierarchies. Diagnoses of feline aggression that involve humans include: 1. - aggression due to lack of socialization 2. - play aggression 3. - fearful aggression 4. - pain aggression 5. - redirected aggression 6. - assertion or status-related aggression. These are the behavioral, functional, phenomenological classifications of aggression. It should be noted that cats, like dogs, can be aggressive because of or as a sequelae to underlying organic disease. Medical rule-outs for feline aggression include hepatoencephalopathy, feline ischemic encephalopathy, lead poisoning, hyperthyroidism, epilepsy, and rabies. To the extent that pain aggression is sometimes associated with illness, it should act as a flag for a possible underlying condition; however, in the sense that the term is used here, the aggression is the result of the pain, not of the underlying condition. 1. Aggression due to a lack of socialization: The effect of exposure during sensitive or developmental periods in young animals has been debated. In the 1950s Scott and Fuller investigated the role of developmental periods within the first few months of dogs' lives on their ability to develop appropriate social behaviors. While these periods, called "sensitive" periods by Bateson exist, they are best viewed in the context of risk assessment. Animals for whom all sensitive period requirements were met can still have problems, and animals who missed socialization for the relevant periods can do well; however, the risk of having problems attendant with the respective socialization or sensitive period increases if exposure during the that period is missed. For example, cats who have not had contact with humans prior to 3 months of age have missed sensitive periods important for the development of normal approach responses to people. Karsh and Karsh and Turner (1988) examined the extent to which the social environment experienced by cats affected their ability to interact with people. Among their findings, which are more fully discussed in the chapter on normal cat behavior, were that cats that were not handled until 14 weeks of age, were fearful and aggressive to people, regardless of the circumstances. These cats would not volitionally approach humans, and were aggressive if they could not escape. In contrast, cats handled for as little as 5 minutes per day from the day they were born until they were 7 weeks of age were quicker to approach and solicit people for interaction and gentle play, were quicker to approach inanimate objects, and were quicker to play with toys. This suggests that there are complex, far-reaching consequences of early interaction with people. Lack of such social interaction with other cats may result in the same lack of normal inquisitive response to other cats. This negative response can be augmented by sub-optimal nutritional conditions for the pregnant queen. Kittens born to such queens generally have a delayed developmental skills in addition decreased ability to learn, and increased (and usually inappropriate) reactivity to novel situations and stimuli, and an inappropriate response to other cats (this is more fully discussed in the chapter on normal feline behavior). The chance of such cats responding normally to most situations involving any interaction is diminishingly small. Furthermore, total isolation from cats can have negative consequences for future interaction with humans. This constellation of deprivation scenarios may be contributory to many of the aggressions seen in urban, feral cats. These cats will never be normal, cuddly pets, although they may attach to one person or a small group of people over a period of time. If forced into a situation involving restraint, confinement, or intimate contact, these animals may become extremely aggressive. 2. Play aggression: Cats who were weaned early and then hand raised by humans may never have learned to temper their play responses. Social play in cats peaks early and is replaced by more predatory activities by weeks 10-12 and by social fighting by week 14. Cats who, as kittens, never learned to modulate their responses may play too aggressively with owners. These cats may not have learned to sheathe their claws or inhibit their bite. 7/27 cats studied by Chapman and Voith (1990) were diagnosed with play aggression. The frequency of this aggression is likely to be directly related to the demographic environment of the cat community - urban practices may have more cats with a history consistent with the development of play aggression. It is not clear if there is a component of oral response associated with an owner who bottle fed the cat. Were the kitten to nurse too hard on the mother or hurt her in play, the mother would have swiftly corrected the kitten. This appears to be less common among owners playing the nursing role, possibly because they are concerned about injuring the kitten. This is a valid concern; however, if they mimic feline behaviors such as neck bites an growls or hisses, the kitten learns to respond and inappropriate play behavior and play aggression may not develop. Should these problems still ensue, they are treatable using behavior modification that interrupts the inappropriate behavior and replaces it with a more appropriate one. For example, the kitten that is playing roughly can be blasted with a water pistol or a compressed air canister at close range to startle it; this is most effective if the startle occurs as the cat is commencing the inappropriate behavior. Then, when the cat seeks out the owner's company, the owner can strike, massage, and provide the cat with food treats whenever it is acting calm. Owners must be vigilant for the first signs of any inappropriate behavior (pupils dilating, claws unsheathed, ears back, legs and shoulders stiffening, tail twitching) and correct the cat using a correction designed to startle as early in the sequence as possible. The startle technique, whether tapping on the nose, blowing in the face or using a water pistol or air canister, should be humane: this means that the lowest level of stimulus that gets the desired effect of aborting the behavior and moving on to another is the one that should be used. 3. Fearful, fear, or fear-induced aggression: Fearfully aggressive cats will hiss, spit, arch their backs, and piloerect, if flight is not possible. Flight, a defensive activity, is virtually always a component of fearful aggression in cats. As they are pursued with increasingly less escape space, cats will draw their head in, crouch, growl, roll on their back if approached (this is NOT a "submissive" behavior in cats - it is an overt, defensive behavior), and paw at the approacher. If the approacher continues his or her pursuit, the fearfully aggressive cat will try to strike at him or her, and follow this with holding the approacher, using the forepaws, while kicking with the pack feet and biting around the neck. Most people who have seen or experienced rough play from cats are also familiar with this sequence of behaviors. When fearful aggression involves other cats, the cats that are fearfully aggressive generally do not seek out the other cat for aggressive interactions. Fearful aggression usually involves a combination of offensive and defensive postures and overt and covert aggressive behaviors (Leyhausen, 1979). There are genetically friendly cats and genetically shy cats. It is unclear the extent to which shy cats have the potential to become fearfully aggressive, but there are cats who, despite the best socialization possible, become aggressive whenever fearful. These cats also may become fearful without an apparent stimulus. Regardless, if threatened, any cat will defend itself. Depending on the outcome of the treat, the cat can learn to become fearfully aggressive. This is particularly important if small children are involved, since they may not know how to appropriately respond to a cat that is crouching. Any animal that is cornered and cannot escape has the potential to attack. It is imperative that the cat not learn that his or her only recourse is aggression since this could lead to them becoming aggressive in response to any approach. Behavior modification can be very effective early in the development of the condition. Pharmacological intervention can be a useful adjuvant. It is not clear if any intervention can be successful if the condition is genetic. 4. Pain aggression: As is true for dogs, cats that are painful, either because of an injury or as a sequelae to an underlying medical condition, can be painful upon manipulation. Practitioners can often induce this type of aggression in injured or arthritic and dysplastic cats. It can often become fearful aggression if it is result of long-term painful treatment. It is a defensive aggression, and will respond to measures that alleviate the pain, and minimize the potential to be exposed to it. Companion animal analgesia is finally receiving the attention it deserves. Appropriate use of such analgesia can minimize painful aggression in any animal. Cats who have gotten their tails caught in doors are often very aggressive whenever anyone attempt to touch their tail. Some of this could be fear, but even when restrained they appear to become aggressive during manipulation. It is possible that they have some long-standing damage that is not apparent in medical and neurological work-ups. Behavior modification designed to teach them to relax and tolerate touching can be useful, as can anti-anxiety medication. The same phenomenon is infrequently reported for cats that have undergone declaw and who now will not use their feet. When their feet are manipulated these cats are, apparently, painfully aggressive. Full work-ups, including radiography, usually reveal no detectable abnormality, leading to discussions of "phantom" pain. Pain is a complex issue and probably under-appreciated in such circumstances. These cats also often respond well to behavior modification designed to teach them to relax and to anti-anxiety medication. If there has been no painful medical intervention and the cat appears to exhibit this behavior, consider abuse. Cats, particularly strays, are good victims for torture, and may represent the first sign that untoward events are occurring in a household where there are children. The role of pain aggression in cat-cat interactions has been under-explored, but, especially when cats are mismatched by size, health status, or temperament, is probably not a trivial problem. This would be particularly true for cats that have already been in fights and may have painful abscesses - any physical contact by another cat may cause them to react defensively in an aggressive manner. 5. Redirected aggression: Redirected aggression is seen in felines, as well as in canines; however, it can be difficult to recognize and may only be reported as incidental to another form of aggression. In redirected aggression, any interruption of an aggressive event between two parties by a third party results in redirection of the aggressive behavior to the third party or to another, uninvolved individual. It is important to realize that the interrupted aggressive event may only be a threat, so that the person (or animal) interrupting it may not realize what is occurring. Cats appear to remain reactive for an extended period of time after being thwarted in an aggressive interaction. Clients need to realize this and to be aware of the subtleties of their behavior that communicate their intent. Since redirected aggression is often precipitated by another inappropriate behavior, it is important to treat that behavior, as well. Treatment involves standard behavior modification techniques. If there is a socially mediated conflict within the household cats, some environmental modification may be necessary to decrease the extent to which the involved cats are capable of interacting. Owners should be encouraged to use inanimate objects (battery operated water pistols, buckets of water, foghorns, et cetera) to intervene between fighting animals. This minimizes danger to the owners and may have the benefit of aborting the behavior while teaching the cat that there are consistent, undesirable consequences to its inappropriate behavior. 6. Assertion or status-related aggression: Assertion or status aggression has been described as the 'leave me alone bite' and most frequently occurs when being petted. The most similar situation in canines is impulse control aggression; however, the divergent evolutionary history of canine and feline social systems argues that these are not homologous situations. These cats share with dogs with similar problems the need for control of the situation. Nothing the owner did provoked the cat; rather the cat demonstrates a desire or need to control when the attention starts and when it ceases. Some cats do this by biting and leaving, while the occasional cat with take the owners's hand with its teeth, but not bite. Fortunately, owners can be taught observe signs of impending aggression (tail flicking, ears flat, pupils, dilated, head hunched, claws possibly unsheathed, stillness or tenseness, low growl) and interrupt the behavior at the first sign of any of these by standing up and letting the cat fall from their lap or abandoning the cat and refusing to interact until the cat is exhibiting an appropriate behavior. Clients should be discouraged from direct physical correction of the cat, since the cat may view that as a challenge and intensify its aggression. If the cat does not respond to passive control or redirects its aggression, it is safer to counter the behavior with a fog horn or a battery operated water pistol. Corrections must occur within the first 30-60 seconds of the onset of the inappropriate behavior to insure learning; corrections within the first second are best. Clients having such cats should be aware that their cats are never going to be hugely cuddly, although, if the client can refrain from petting them, they may be willing to sit quietly on the owner's lap for extended periods. A few words on intercat aggression: Intercat aggression is common between toms. In most wild, feline social systems, few males mate with most of the females. The skewed sex ratio in the breeding population is induced and maintained by vigilance and aggression on the part of the males. There is an additional olfactory component of spraying and non-spraying marking that contribute to the rank aggression. The aggression is classic and involves flattened ears, howling, hissing, piloerection, threats using eyes, teeth, and claws an combat. Early neutering (prior to 12 months of age) decreases or prevents fighting by 90%. It is not clear if very early spaying and neutering programs would further reduce this, but given the hormonal facilitation of the aggression one would hypothesize that this would be the case. Intercat aggression is more commonly based on conflicts within social hierarchies than it is with sex. Cats begin to become socially mature some where between 2 and 4 years of age. At this time, some cats may begin to challenge others. Problems arise when one cat will not accept lack of engagement by another cat. Responses include passive aggression (staring and posturing), active aggression, and marking. Cats that consider themselves as more equal are less likely to participate in overt aggression - expect covert aggression. Intercat aggression is extremely complex, often subtle, and under-appreciated. Elimination disorders, stress, and environmental enrichment: The social system and extent to which olfactory communication factors into it, may create some potential conflict when cats have little control over their social and physical environments. In free-ranging situations, most of the cats with whom domestic cats associated are known to them, raised with them, may be more related to them than is true for the average cat household, and, when unrelated, may become more known to them over a longer time than is true when additional cats are introduced into standard pet households. Also, behaviors that free-ranging domestic cats exhibit (e.g., spraying on frequently used trails, scratching within home ranges, et cetera) may not be tolerated within the enclosure of a home environment. Because of differences in our historic and evolutionary relationships with dogs and cats, we have to remember that humans never exerted any selection on cats to shape behavior. This contrasts dramatically with out relationship with dogs where virtually all of our selection was on and for specific behaviors or suites of behaviors. It's important to repeat and remember that the story of our relationships with cats was a fortuitous one associated with disease control. Our relationship with dogs was a deliberate one associated with almost identical social and signaling systems that allowed us to select behaviors and breeds on the basis of work. Given this, we should not be surprised that when cats are given less space and less freedom, events that we perceive as behavioral problems occur, and many of these involve olfaction. This is not to say that some cats are not truly "abnormal" and that no matter what the environment is, they will have problems. These cats exist, but the threshold for stress-related behavior problems should be different than that for dogs specifically because of our historic relationship with them, and the extent to which we have not selected for or modified their behavior over time. The most common ways that environmental stress or distress appears in cats is in elimination disorders. Feline elimination disorders: The most common feline behavioral problems involve inappropriate elimination behavior. This inappropriate behavior can take the following forms: substrate or location aversion, substrate preference for urination, defecation, or both, location preference for urination, defecation, or both, and spraying. This is one set of behavioral problems that requires a substantial medical work-up and rigorous follow-up. 1. Aversions to substrates or location can be difficult to distinguish from preferences, and invariably lead to the cat choosing another location or substrate for elimination. It may never be clear why the cat has developed an aversion to one location or one substrate; when this occurs it becomes apparent because of the cat's total avoidance of the offending area or surface. In cases involving aversions that have developed in response to an horrific experience, some owners have reported that the animal will hiss, growl, slink, or piloerect when found in proximity to the substrate or area. Declawing coupled with premature return to gravelly kitty litter has been implicated in the development of some aversions to substrate. For ultra fastidious cats, vomit or diarrhea, either their own, or a house mate's, may induce the same response. Location aversions are more often coupled to fearful or painful situations, such as injuries caused by doors or torment from another cat or a child. If a cat is absolutely avoiding a specific area or substrate for elimination, they will find another until they are presented with suitable options. This is discussed below in the specific preference categories. 2. Substrate preferences for elimination are extremely common, particularly among long haired cats. This means that the cat prefers some other substrate than its litter for elimination. Although the substrate preferred is usually softer (sheets, underwear, bath mats, plastic trash bags), this does not have to be so, and some cats prefer open, reflective areas such as linoleum, wood floors, tiles, and bathtubs. The ancestral and wild condition for elimination in felids resembles the latter. This problem can develop spontaneously or be induced. Many owners complain of the problem after an extended vacation where someone fed their cat, but would not change the litter. The cat is repulsed by the filthy litter, seeks another area from desperation, and discovers that it prefers this substrate. Illness can also be implicated in the development of a preference; a cat with cystitis or diarrhea may not be able to make it to the litter box and in the process of covering up the urine or feces on the carpet, discovers that it likes carpeting. Cats who a reintroduced to hard litter too soon after declaw frequently develop a substrate aversion and subsequently identify a new preference. Treatment involves environmental and behavioral modification and may require pharmacological intervention. First, a physical exam is essential. This must include a complete urinalysis or fecal, depending on the nature of the problem, and might include blood work. A large number of cats (estimates hover around 1/3) with substrate preferences who either do not respond, or start to respond to environmental and behavioral modification and then relapse have apparent or occult UTIs. If the fecal/UA is positive, treat and suggest environmental/behavioral modifications, also, since as a result of the illness the cat could have shifted his preference. 3. Location preferences require many of the same strategies as for substrate preferences, especially since many location preferences appear to be mixed substrate preferences. In a true location preference, the cat prefers one or a few areas for urination or defecation; none of these is generally its litter box. Cleaning and covering should be done as above. Then, a litter box with a litter the cat likes can be placed in the area. If the cat starts to use it, terrific. After a week or two the box can be slowly (1-2 inches per day) moved to a more appropriate area. The client should watch for relapses or sneaky elimination in new spots. If this doesn't work, the cat may respond to counter-conditioning: food dishes can be placed in the affected areas. Generally, cats will not eliminate where they are fed. Some will. If the number of locations is great, this will not work. If it is possible to rearrange the furniture so that the cat's favorite spot is covered, this should be done. Sometimes the cat shifts its spot; often this is suggestive of a mixed substrate preference. An in depth history of every area ever used for elimination is essential. Confinement and the protocol above should then be implemented. A note on cleaning: all layers must be cleaned. If the problem has been ongoing for some time the odor has soaked through the floor. In some cases floor boards need to be replaced, as does carpeting and padding. This is especially true if subfloors are involved. 4. Spraying can be done by male or female, intact or neutered animals. Clients often confuse spraying with urination. Encourage them to describe postures and note locations. If the cat is standing, wiggling its tail with a look of bliss on its face it is spraying. Sprayed urine hits vertical surfaces and drips down. Cats can also stand in the middle of a horizontal surface, such as a bed, a spray, in which case they will leave a long, thin wet area, rather than a puddle. Have clients crawl on their hands and knees over every inch of carpet; if there is urine in a puddle in the middle, but no where else, the cat is not spraying. Spraying can be triggered by hormones, in the affected cat or another in the household, by the addition of a new animal, by the visitation of a strange cat to windows or sliding glass doors, by partial obstructions, by seasonal changes, and by events only understood by cats. The above protocol for cleaning and litter box care should be followed. Many cats will spray against the inside of covered boxes. Regardless, the key to treating spraying is pharmacological. First, any underlying medical cause (FLUTD, cystitis, UTI, obstruction, anatomical abnormalities) must be ruled out. Should there be no apparent medical cause treatment can proceed with diazepam (1.0-3.0 mg per cat q 12-24 h.). Diazepam, when used correctly, will control spraying in 75-90% of all cats. Generally, cats for whom it is successful will stagger mildly, with impaired depth perception for a few days; staggering should resolve spontaneously by the end of the week. Some cats may need to be on diazepam for a few weeks, some seasonally, some forever. The lowest effective dose should be used. Some cats who do respond to diazepam require a benzodiazepine with a longer half-life. Clorazepate dipotassium (Tranxene SD) at 0.55-2.2 mg per kg prn can be used; however, if the cat did not respond to diazepam, it may not respond to this. A few cautionary notes regarding benzodiazepines. Clients should be cautioned that this is a humanly abusable drug. Clearly, some clients should not be given diazepam for their cat since it provides them with ready access to a controlled substance. While the cats do not get "hooked", a fear of many clients, blood work should be instituted on a regular basis to check for iatrogenic disturbances if the animal is on any drug for any length of time. There is some recent concern that the exceptional cat may develop hepatic failure when exposed to benzodiazepines. This needs to be more fully investigated and clients should be advised to watch for any signs of hepatopathy. Tricyclic antidepressants (TCAs) act to inhibit serotonin re-uptake, and can be useful for some cats that spray, some who are averse to or anxious about their litter box, and cats who are experiencing anxiety about heir social situation. Drugs of choice include amitriptyline and its active intermediate metabolite, nortriptyline ( both at 0.5-1 mg/kg po q. 12-24 h). Clomipramine (Anafranil) (0.5 mg / kg po q. 24 h x 6-8 weeks to start) can be an excellent drug for spraying, and is more specific in its serotonin re-uptake properties, as can the selective serotonin re-uptake inhibitors including paroxetine (Paxil) and fluoxetine (Prozac) [both at 0.5 mg / kg po q. 24 h x 6-8 weeks to start). Buspirone (BuSpar) is a newer non-specific anxiolytic. In cases where benzodiazepines and, or progestins fail it has been successful in controlling spraying, even in cats for whom spraying is associated with intercat aggression. It appears to have comparable side effects of many anti-anxiety drugs and owners should be warned that potential side effects include inappetence, lethargy, and possible interference with thyroid medication. If the symptoms are not transient, the drug should be withdrawn. The dose is 2.5-5 mg per cat q. 8-12 h.. The rationale for trying this drug latter, rather than earlier includes its cost and the fact that we just don't know as much about it in small animals as we do the other drugs. This will change in the next few years and the cost is not prohibitive for an animal a small as a cat. The new treatment involving a synthetic analogue of feline cheek gland secretions (e.g, pheromones) (Feliway™; Abbott Laboratories) may show some promise for spraying that either has recently started and is related to the introduction of a new individual (human or animal), or to disruptions in the colony scent. No double-blind studies have been conducted, and the need for such studies is more critical in this situation than in those involving some oral medications because of the manner in which the pheromone is applied and the need for clients to be cautious in their interpretations. One study that has examined the use of Feliway for the treatment of spraying found that in many cases there was a statistically significant reduction in spraying, but few to no cats stopped spraying all together. That's to be expected if the problem is about anxiety and not about the actual pheromonal environment. In some cases the concomitant use of pheromonal agents and anti-anxiety medications may produce a quicker resolution than would be produced by either alone. The neurochemical mechanism by which such pheromonal sprays may work is unknown, but it might be worthwhile, given the data, to explore the extent to which pheromones can act as aerosolizable anxiolytics. Environmental enrichment: In part, because of the associations between elimination disorders and intercat aggression, a critical part of treatment should be to 'expand' and enrich the cats' environment. Even indoor cats can have their environment 'expanded' by adding 3-dimensional surfaces, interactive toys and scratching areas, and by the creating of food puzzles. Because cats will time- and space-share the extent to which the environment is made more complex is limited only by the client's imagination. Given that in a free ranging situation cats will use between 0.5 and 990 hectares in the course of normal social interactions, it is incumbent upon clients with indoor cats to insure that the cats have a similarly challenging home environment. Ladders, boxes, kitty condos, outdoor or window enclosures, and interactive food toys can also help. Because domestic cats are largely solitary hunters getting one or two small meals a day, our way of feeding cats is tremendously abnormal, and may be responsible for the obesity epidemic in household cats. Food puzzles can be very easily created using large trays and rocks or flower pots and hiding the food within them. If the food is kibble, it can be located in small piles in a variety of areas for which the cat must work to get it (e.g., in a flower pot on a windowsill, under a "toad hole" on an upper ladder or book case, et cetera). The only caveat for the latter is that the clients must remember when the food is so that they don't have a problem with rodents or freshness, and they must insure that caching food does not create a behavioral problem. References:
Real behavior mod Introduction Behavior modification is nothing more than the process of altering an animal's behavior. The classic client and veterinarian response to having "behavior mod" recommended as part of a treatment plan is to exclaim that they "don't have time for that". What is not understood here is that we engage in behavior modification either actively or passively every hour of the day and in everything we do. The basic tenets of behavior modification treatment are not complex, and are put into action whether or not we consciously acknowledge or recognize that this is so. Accordingly, clients are often unconsciously and accidentally employing principles associated with learning and behavior mod, and inadvertently doing an excellent job of reinforcing the behaviors about which they are most distressed!! Our focus should be to help clients understand that learning occurs all the time and that we can shape the direction, rate, and complexity of the learning process with conscious effort. This does not mean that the clients 'must' engage in complex active behavior mod. It does mean that they can use small, relatively passive techniques to effect huge changes. Clients' fears People are also afraid of the terms used in behavior mod: desensitization, counter-conditioning, conditioned stimulus, et cetera. These are jargon - anyone who is competent can teach clients to change their pets' behaviors without having to resort to these terms, and while implementing the concepts. The key to clear communication is to lose the jargon and concentrate on content. Potential problems The problem with changing any behavior is 2 fold: (1) inertia is a powerful force, and (2) breaking behaviors down into elements that require change and understanding how to change them can be difficult to do. This difficulty lies in understanding exactly what is called for in the behavior modification technique of choice and in the timing of the client's response to the dog's behavior and communicatory gestures. Before any client can change any animal's behavior - or their own - they MUST recognize (1) what normal signaling is (1), (2) what signals are associated with the problem they wish to change, and (3) what signals precede # 2. Although we ask clients to 'intervene' and - minimally - interrupt the behavior in step (3), intervention is deliberately left undefined. In any situation there are three environments available for intervention which can be potentially modified: the physical environment, the behavioral environment, and the pharmacological environment. These environments are not independent. The key to understanding how dogs learn is to appreciate the complexity of interaction between these environments, and the importance of factors affecting temporal and intensity changes and interactions within these environments. Keys to success Keys to successful implementation of behavior modification include the following (2): (1) The clients must cease their own exhibition of any behaviors or behavioral sequences that promote, trigger, cause, encourage, or correlate with any of the behaviors in the dog or cat that they wish to change. (2) The clients must commit to clear signaling and a humane and possible set of rules by which they can interact with the cat or dog. (3) The signals in (2) must have a canine or feline equivalent so that the dog or cat both can understand and have the mental space to understand what the client wants. For example, sitting in dogs and cats is a 'stop' behavior, and in dogs this is a deferential behavior that functionally passes the job of giving the next signal back to the individual who engendered the 'sit'. (4) The behavior mod - which is a true rule structure - should be sufficient either signal to the dog or cat what they can expect to happen next or to teach them that they can look to the client for all cues about the appropriateness of their behavior if they are concerned. (5) The reward structure - which is another rule structure - should be clearly defined and appropriately reinforced at all times. Clients need to understand at their gut level that we teach best by rewarding every instance of appropriate behavior and that we retain what we have learned best by rewarding intermittently. Clients also need to understand that intermittent is NOT synonymous with 'seldom". (6) Unless the client's intent is to teach the dog or cat to fear them, to teach the pet what will only engender dissatisfaction, or to confuse the pet, clients MUST stop all punishment, shrieking, yelling, throwing things, et cetera, no matter how good it feels to them. Important points about behavior mod that should go without saying, but don't The following important points regarding behavior modification exercises are those which are most frequently misunderstood by clients and vets, alike. 1. Behavior modification exercises are NOT, repeat NOT, obedience exercises. At the very outset clients should be disabused of the notion that this is fancy obedience. First, while sitting is part of obedience training, the goal of these programs is not just to have the dog sit, but to relax and be receptive to changing his or her behavior while doing so. It is critical that clients understand and appreciate this difference. Dogs that are stressed or anxious cannot successfully learn a more appropriate behavior and they certainly cannot associate that behavior with having fun or with good things happening. Second, if the client perceives that all we are doing is trying to teach the dog what he or she has already learned in training class they will not see the need to comply. If we offer nothing different, what is the point of behavior modification? It is the practitioner's job to teach the client that behavior modification is about changing the way the dog thinks about interactions by rewarding the physical cues associated with the underlying physiological state. Obedience training, while sharing many similarities with behavior modification, differs in the premise, interactive reward structure, goal, and outcome. Most of the dogs that undergo behavior modification have been through some form of training and most know how to sit. For a dog to do this successfully in a class (or even a show) situation, the dog does not have to be relaxed. For behavior mod to work as well as it can the dog MUST be relaxed. 2. Relaxation is key here - the sitting and staying is merely a facilitator for the relaxation response. There is no sense to having the dog sit and stay if it is panting, salivating, its pupils are dilated, its ears are back, and it is clearly distressed. What on earth is the dog learning? It's simple - the dog is learning to be more distressed - while sitting - and also teaching his- or herself to become refractory to complex learning because of arousal of the HPA-axis (hypothalamic-pituitary-adrenal axis) (4, 5). This is why old-fashioned, out-moded, and simplistic 'sit-stay' programs so often fail: the dog sits, but is still distressed. 3. Clients will have trouble with appropriate timing of rewards and 'corrections'. 'Corrections' should be restricted to walking away from the dog or a quick, low vocal signal that the dog is behaving undesirably. The point of the 'correction' is to interrupt the dog - not to 'get even'. If clients are doing any more than this, they are at risk for potentially - albeit accidentally - exhibiting abusive behaviors that will make the dog worse. Dogs read non-vocal or body language far better than do most humans (6-8). It is easy for them to 'subvert' the exercise and shape the behavior of the client. Problem dogs have been doing this already, and such behaviors are NOT malicious. They ARE, however, behaviors that logically are exhibited by a confused, uncertain animal in an attempt to gain information about what can be expected - and what their response should be - within that context. Because clients so often attribute uncharitable 'motivations' to their pets someone from the outside of the relationship needs to be able to comment on timing problems and to instruct the clients when to change their posture, their tone, or their quickness of praise or reward. Most clients are quite good at learning to do this, but they need help. After the initial demonstration they may even need to be able to show you what they are doing to see if it is correct, or if you can make recommendations. This can be done in a quick 10-15 appointment (and support staff can be responsible for this), or the client can send a video, and an appointment - in person or by telephone - can be set for a critique. If the clients are not seeing an improvement, or are having an actual problem either:
3. The practitioner and, or the staff must work WITH the client. In the case of a very fearful or very aggressive dog the practitioner may not be able to demonstrate the exercises or fit a halter during the first visit. In such cases, after fully cautioning the client about possible risks, the practitioner can ask if the client feels comfortable attempting the first round of the behavior modification protocols while the practitioner talks them through it. For reasons of liability it is important to explain that this is not the desired technique; however, if the client cannot eventually work with the dog, or if the client is perpetually afraid of the dog, the situation will be hopeless. If the practitioner is able to work with the dog, they should do so both to teach the dog the appropriate behaviors and to demonstrate to the clients what is desired. Again, making a video that can be played back and critiqued after the session can help. When the dog works well with the practitioner, it is the client's turn.It is not sufficient to demonstrate the behavior modification without then giving the client the chance for emulation. It is of no use if the dog is perfect for the practitioner, but a horror for the client. -- the practitioner does not have to go home and live with the dog. The clients must be able to accomplish the suggested modification, hence it is inappropriate to just send them home with sheets of paper. If the client's dog cannot or will not work with the practitioner, the practitioner should have another dog available that can be used. This dog should be able to work with the client so that the client understands what an appropriate response is. Everyone who is serious about veterinary behavioral medicine should have a demo dog who will teach the clients and staff to hone their observational and functional skills. Alternatively, these tasks can be farmed out to someone more likely to have a good demo dog and who is uniquely equipped to teach the practical implementation of behavior modification: an Association of Pet Dog Trainers (APDT) Certified Pet Dog Trainer (CPDT) (www.apdt.com). 4. Finally, if there is the potential for a dangerous behavior that will need to be altered or avoided, it would be optimal if the client doesn't discover this when there is no one to help them. A run-through of the program will minimize, but not ablate, this chance. A few words about rewards: Most commonly used behavior modification programs employ praise and food treats or other rewards. The higher the quality of the treat the better the dog's response. A dog who might work for American cheese while on the property, might need dried liver when out in traffic. No one goes to hell for using food treats, but to hear people's reactions, you'd be certain this was the case. The approach to behavior modification discussed here does not use hand signals or clickers. Clickers are unforgiving with respect to timing, and to ask a client to read a problem pet's signals, monitor them constantly, teach them to sit and relax, and incorporate the clicker system of secondary reinforcement into behavior mod, is not kind to the clients, and can further confuse the dog. Hand signals are commonly used in obedience and can be useful for dogs and clients, but behavioral patients need every bit of help that they can get. Hand signals, here, will be a needless distraction. Once the dogs master the programs, they will have no problems coupling the learned vocal cues to visual ones. Until then, these dogs should work in calm, quiet circumstances, without distraction, for vocal cues, and a consistent reward structure. Dogs can learn all the words for the 'commands', signals, or requests that they will need for these programs. Most importantly, hand signals at this stage will only ask the dog to distract their attention from the behavior modification process, and, for very aggressive dogs, such signals will put the person using them at risk. Without exception, dangling body parts in front of an aggressive dog is not recommended, and will make the animal more anxious. In a worst-case scenario, hand signals can be seen by the dog as threats. Tips for incorporating behavior mod into everyday life for ALL of your clients: (1) Don't single out only your problem patients for behavior mod. Wouldn't ALL of them benefit from learning to be calm as a way of seeking information from you or the client? (2) Cats should learn behavior mod, too. (3) At every single visit, teach the pet something behavioral. This is simple: ask them to sit, cock their head, and look at you for a food treat. Voila! Magic! (4) Practice 3. (5) Have the clients practice 3 with all of their dogs and cats: if any pet wants love, food, affection, water, grooming, to play fetch, to get into the car, et cetera - encourage them to sit and look at you or the clients first. In turn you - and the client - must be quiet and look at the pet. Acknowledge the signaling relationship and be clear (this works for spouses and kids, too). Then give the pet access to that which they requested. (6) Every member of your staff should already be practicing 3. If they are not doing so, why not? (7) Fit all pets with head collars and harnesses. Stock and sell these AND the know-how that goes with using them. Throw out: chain leashes, choke chains, prong collars, slip collars, et cetera. (8) Teach clients how to pet their dogs and cats. It's so simple it will just plumb elude them. Ask them what they want: a jazzed, reactive pet, or a calm one.......logic will carry them from here. (9) Reward spontaneously wonderful behaviors and teach your clients to do so by example. [Thanks for paying attention to these notes!] (10) Encourage gentle walking on a leash by engaging the pet in conversation....encourage your clients to avoid learning that which must be unlearned later (for them and the pet). This translates to the over-used concept of preventing - not treating - problems. While a bit overused, the concept is valid: all management related problems can be prevented by telling the animal what you want in advance and encouraging those favored behaviors. (11) Be reliable, signal clearly, be compassionate and humane, and let your patients make you a better person. Then pass it on to the clients. Dogs and cats are highly cognitive animals (9,10). If you realize this and incorporate behavior modification designed to take advantage of their cognitive skills at each and every routine appointment, you may have no real behavior cases in your practice. References:
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