Improved neurocognitive performance in FIV infected cats following treatment with the p75 neurotrophin receptor ligand LM11A-31.

HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective treatment options. Neurotrophin based therapies have excellent potential to stabilize and repair the nervous system. A novel non-peptide ligand, LM11A-31, that targets the p75 neurotrophin receptor (p75NTR) has been identified as a small bioavailable molecule capable of strong neuroprotection with minimal side effects. To evaluate the neuroprotective effects of LM11A-31 in a natural infection model, we treated cats chronically infected with feline immunodeficiency virus (FIV) with 13 mg/kg LM11A-31 twice daily over a period of 10 weeks and assessed effects on cognitive functions, open field behaviors, activity, sensory thresholds, plasma FIV, cerebrospinal fluid (CSF) FIV, peripheral blood mononuclear cell provirus, CD4 and CD8 cell counts and general physiology. Between 12 and 18 months post-inoculation, cats began to show signs of neural dysfunction in T maze testing and novel object recognition, which were prevented by LM11A-31 treatment. Anxiety-like behavior was reduced in the open field and no changes were seen in sensory thresholds. Systemic FIV titers were unaffected but treated cats exhibited a log drop in CSF FIV titers. No significant adverse effects were observed under all conditions. The data indicate that LM11A-31 is likely to be a potent adjunctive treatment for the control of neurodegeneration in HIV infected individuals.

Enrichment Preferences of FIV-Infected and Uninfected Laboratory-Housed Cats.

Environmental enrichment is critical for alleviating stress in laboratory felines. However, there is a paucity of information about suitable enrichment for cats. This study aimed to determine preferred enrichment options of individually-housed, castrated male domestic short hair cats (Felis catus) used in a longitudinal study of the effects of chronic feline immunodeficiency virus (FIV) infection, and to determine if the FIV status of the cats affected enrichment preferences. Preference testing was performed with two types of grooming brushes, three different interactive play options, including a laser, ball, and petting interaction with a familiar investigator, and two types of toenail conditioning objects. We found that cats elected to be brushed, preferred social interaction and play with the laser to the ball, and preferred to scratch on an inclined-box toenail conditioning object compared to a horizontal, circular toenail conditioning object. There were individual preferences for enrichment opportunities. There were no differences in preferences between FIV-infected and sham-infected cats. These enrichment preferences may be used to advise laboratory animal facilities and researchers about how to best accommodate the behavioral needs of laboratory cats.

Use of single-dose oral gabapentin to attenuate fear responses in cage-trap confined community cats: a double-blind, placebo-controlled field trial.

Objectives This double-blind, placebo-controlled study evaluated the safety and efficacy of single-dose oral gabapentin administered for the attenuation of fear responses in cage-trap confined community cats. Methods Community cats presented in cage traps for trap-neuter-return (TNR) were recruited and screened for inclusion. Each enrolled cat was randomly assigned and administered one of three equal-volume, single-dose treatments: placebo, low-dose gabapentin (50 mg) or high-dose gabapentin (100 mg). At baseline, 1, 2, 3 and 12 h post-administration, a single, blinded observer scored each cat for signs of fear and sedation using published paradigms, calculated the respiratory rate and documented any observable facial injuries. Results Fifty-three cats met the inclusion criteria and completed the study. Cat stress score (a measure of fear) was lower in cats that received gabapentin (50 or 100 mg) than in cats that received placebo (50 mg: P = 0.027; 100 mg: P = 0.029), with the greatest reduction at 2 h post-treatment ( P = 0.0007). Respiratory rates did not differ between treatment groups. There was no difference in sedation scores between the groups ( P = 0.86) at any time point ( P = 0.09). Cat facial injuries did not vary by treatment group or over time. No adverse effects were detected specific to gabapentin administration. At 1 h, hypersalivation was observed in four cats across all treatment groups. All cats recovered from surgery and anesthesia uneventfully. Conclusions and relevance This study supports the hypothesis that 50 mg or 100 mg gabapentin (9.2-47.6 mg/kg per cat) reduces fear responses in confined community cats without measurable sedation over 3 h post-administration vs placebo. Gabapentin treatment was well tolerated in this population of cats. Further studies are recommended to investigate the use of oral gabapentin earlier in the TNR process, such as immediately after trapping or prior to transport for the prevention of confinement-related injuries.

Endogenous Oxytocin, Vasopressin, and Aggression in Domestic Dogs.

Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT) and vasopressin (AVP)-neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species-and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs) for the measurement of free (unbound) and total (free + bound) OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.

Effect of Wearing a Telemetry Jacket on Behavioral and Physiologic Parameters of Dogs in the Open-Field Test.

Safety pharmacology studies in dogs often integrate behavioral assessments made using video recording with physiologic measurements collected by telemetry. However, whether merely wearing the telemetry vest affects canine behavior and other parameters has not been evaluated. This pilot study assessed the effect of a telemetry vest on behavioral and physiologic responses to an environmental stressor, the sounds of a thunderstorm, in Labrador retrievers. Dogs were assigned to one of 2 experimental groups (Vest and No-Vest, n = 8 dogs per group) by using a matched pairs design, with a previously determined, sound-associated anxiety score as the blocking variable. Dogs were individually retested with the same standardized sound stimulus (thunderstorm) in an open-field arena, and their behavioral responses were video recorded. Video analysis of locomotor activity and anxiety-related behavior and manual determination of heart rate and body temperature were performed; results were compared between groups. Vest wearing did not affect total locomotor activity or rectal body temperature but significantly decreased heart rate by 8% and overall mean anxiety score by 34% during open-field test sessions. Our results suggest that the use of telemetry vests in dogs influences the measurement of physiologic parameters and behaviors that are assessed in safety pharmacology studies.

Effect of Wearing a Telemetry Jacket on Behavioral and Physiologic Parameters of Dogs in the Open­Field Test.

Safety pharmacology studies in dogs often integrate behavioral assessments made using video recording with physiologicmeasurements collected by telemetry. However, whether merely wearing the telemetry vest affects canine behavior and otherparameters has not been evaluated. This pilot study assessed the effect of a telemetry vest on behavioral and physiologic responses to an environmental stressor, the sounds of a thunderstorm, in Labrador retrievers. Dogs were assigned to one of 2 experimental groups (Vest and No-Vest, n = 8 dogs per group) by using a matched pairs design, with a previously determined,sound-associated anxiety score as the blocking variable. Dogs were individually retested with the same standardized soundstimulus (thunderstorm) in an open-field arena, and their behavioral responses were video recorded. Video analysis of locomotor activity and anxiety-related behavior and manual determination of heart rate and body temperature were performed;results were compared between groups. Vest wearing did not affect total locomotor activity or rectal body temperature butsignificantly decreased heart rate by 8% and overall mean anxiety score by 34% during open-field test sessions. Our results suggest that the use of telemetry vests in dogs influences the measurement of physiologic parameters and behaviors that areassessed in safety pharmacology studies.

Efficacy of a single dose of trazodone hydrochloride given to cats prior to veterinary visits to reduce signs of transport- and examination-related anxiety.

OBJECTIVE To evaluate the efficacy of a single dose of trazodone for reducing anxiety in cats during transport to a veterinary hospital and facilitating handling during veterinary examination. DESIGN Double-blind, placebo-controlled, randomized crossover study. ANIMALS 10 healthy client-owned cats (2 to 12 years of age) with a history of anxiety during transport or veterinary examination. PROCEDURES Each cat was randomly assigned to first receive trazodone hydrochloride (50 mg) or a placebo PO. The assigned treatment was administered, and each cat was placed in a carrier and transported by car to a veterinary clinic, where it received a structured veterinary examination. Owners scored their cat's signs of anxiety before, during, and after transport and examination. The veterinarian also assessed signs of anxiety during examination. After a 1- to 3-week washout period, each cat received the opposite treatment and the protocol was repeated. RESULTS Compared with placebo, trazodone resulted in a significant improvement in the cats' signs of anxiety during transport. Veterinarian and owner scores for ease of handling during veterinary examination also improved with trazodone versus the placebo. No significant differences were identified between treatments in heart rate or other physiologic variables. The most common adverse event related to trazodone administration was signs of sleepiness. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of a single dose of trazodone to cats prior to a veterinary visit resulted in fewer signs of transport- and examination-related anxiety than did a placebo and was generally well tolerated by most cats. Use of trazodone in this manner may promote veterinary visits and, consequently, enhance cat welfare.

Use of oral trazodone for sedation in cats: a pilot study.

OBJECTIVES: Resistance to transportation and stressful veterinary visits are major causes for a decrease in feline veterinary care. Few options exist for oral sedatives to reduce cats' anxiety prior to veterinary visits. The purpose of this study was to evaluate the safety and efficacy of oral trazodone for use as a single dose agent for sedation in cats. METHODS: Six laboratory cats were given single 50, 75 and 100 mg doses of trazodone and placebo. Trazodone 100 mg and placebo treatments were randomized. Pre- and post-study laboratory values and physical examinations were compared. During each 4 h period post-treatment, sedation was measured via accelerometers and video observations scored by an observer blinded to treatment. Examinations were performed on the cats 90 mins after treatment, and their behavioral responses scored by the same blinded observer. RESULTS: No adverse effects or changes in physical examinations or laboratory values were detected as a result of trazodone administration. Accelerometer data showed trazodone 50, 75 and 100 mg caused sedation as measured by activity reduction (83%, 46% and 66%, respectively). In contrast, there was a 14% activity increase after placebo. There was a significant reduction in video observation scores when cats were given trazodone 100 mg compared with placebo. Mean latency to peak sedation for trazodone 100 mg occurred at 2 h. Scores for behavioral response to examination, performed at 90 mins post-treatment, were not significantly different between cats receiving trazodone 100 mg and placebo. CONCLUSIONS AND RELEVANCE: Trazodone was well tolerated in this population of cats and caused appreciable sedation at all doses. Behavior during examination was not significantly different when cats received trazodone 100 mg compared with placebo. Further studies are recommended to investigate the use of oral trazodone in cats for the purpose of decreasing anxiety assocaited with transportation and examination.

The Use of an Open Field Model to Assess Sound-Induced Fear and Anxiety Associated Behaviors in Labrador Retrievers.

Previous studies have shown that the playing of thunderstorm recordings during an open-field task elicits fearful or anxious responses in adult beagles. The goal of our study was to apply this open field test to assess sound-induced behaviors in Labrador retrievers drawn from a pool of candidate improvised explosive devices (IED)-detection dogs. Being robust to fear-inducing sounds and recovering quickly is a critical requirement of these military working dogs. This study presented male and female dogs, with 3 minutes of either ambient noise (Days 1, 3 and 5), recorded thunderstorm (Day 2), or gunfire (Day 4) sounds in an open field arena. Behavioral and physiological responses were assessed and compared to control (ambient noise) periods. An observer blinded to sound treatment analyzed video records of the 9-minute daily test sessions. Additional assessments included measurement of distance traveled (activity), heart rate, body temperature, and salivary cortisol concentrations. Overall, there was a decline in distance traveled and heart rate within each day and over the five-day test period, suggesting that dogs habituated to the open field arena. Behavioral postures and expressions were assessed using a standardized rubric to score behaviors linked to canine fear and anxiety. These fear/anxiety scores were used to evaluate changes in behaviors following exposure to a sound stressor. Compared to control periods, there was an overall increase in fear/anxiety scores during thunderstorm and gunfire sound stimuli treatment periods. Fear/anxiety scores were correlated with distance traveled, and heart rate. Fear/anxiety scores in response to thunderstorm and gunfire were correlated. Dogs showed higher fear/anxiety scores during periods after the sound stimuli compared to control periods. In general, candidate IED-detection Labrador retrievers responded to sound stimuli and recovered quickly, although dogs stratified in their response to sound stimuli. Some dogs were robust to fear/anxiety responses. The results suggest that the open field sound test may be a useful method to evaluate the suitability of dogs for IED-detection training.

Olfactory discrimination and generalization of ammonium nitrate and structurally related odorants in Labrador retrievers.

A critical aspect of canine explosive detection involves the animal's ability respond to novel, untrained odors based on prior experience with training odors. In the current study, adult Labrador retrievers (N = 15) were initially trained to discriminate between a rewarded odor (vanillin) and an unrewarded odor (ethanol) by manipulating scented objects with their nose in order to receive a food reward using a canine-adapted discrimination training apparatus. All dogs successfully learned this olfactory discrimination task (≥80 % correct in a mean of 296 trials). Next, dogs were trained on an ammonium nitrate (AN, NH4NO3) olfactory discrimination task [acquired in 60-240 trials, with a mean (±SEM) number of trials to criterion of 120.0 ± 15.6] and then tested for their ability to respond to untrained ammonium- and/or nitrate-containing chemicals as well as variants of AN compounds. Dogs did not respond to sodium nitrate or ammonium sulfate compounds at rates significantly higher than chance (58.8 ± 4.5 and 57.7 ± 3.3 % correct, respectively). Transfer performance to fertilizer-grade AN, AN mixed in Iraqi soil, and AN and flaked aluminum was significantly higher than chance (66.7 ± 3.2, 73.3 ± 4.0, 68.9 ± 4.0 % correct, respectively); however, substantial individual differences were observed. Only 53, 60, and 64 % of dogs had a correct response rate with fertilizer-grade AN, AN and Iraqi soil, and AN and flaked aluminum, respectively, that were greater than chance. Our results suggest that dogs do not readily generalize from AN to similar AN-based odorants at reliable levels desired for explosive detection dogs and that performance varies significantly within Labrador retrievers selected for an explosive detection program.

Use of trazodone to facilitate postsurgical confinement in dogs.

OBJECTIVE: To investigate the safety and efficacy of oral administration of the serotonin antagonist and reuptake inhibitor trazodone hydrochloride to facilitate confinement and calming after orthopedic surgery in dogs. DESIGN: Prospective open-label clinical trial. ANIMALS: 36 client-owned dogs that underwent orthopedic surgery. PROCEDURES: Starting the day after surgery, dogs were administered trazodone (approx 3.5 mg/kg [1.6 mg/lb], PO, q 12 h) with tramadol (4 to 6 mg/kg [1.8 to 2.7 mg/lb], PO, q 8 to 12 h) for pain management. After 3 days, administration of tramadol was discontinued, and the trazodone dosage was increased (approx 7 mg/kg [3.2 mg/lb], PO, q 12 h) and maintained for at least 4 weeks. If needed, trazodone dosage was increased (7 to 10 mg/kg [3.2 to 4.5 mg/lb], PO, q 8 h). Owners completed electronic surveys rating their dogs' confinement tolerance, calmness or hyperactivity level, and responses to specific provocative situations prior to surgery and 1, 2, 3, and 4 weeks after surgery and at the postsurgery evaluation (at 8 to 12 weeks). RESULTS: Most (32/36 [89%]) of owners reported that their dogs, when given trazodone during the 8 to 12 weeks following orthopedic surgery, improved moderately or extremely with regard to confinement tolerance and calmness. Trazodone was well tolerated, even in combination with NSAIDs, antimicrobials, and other medications; no dogs were withdrawn from the study because of adverse reactions. Owner-reported median onset of action of trazodone was 31 to 45 minutes, and median duration of action was ≥ 4 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that oral administration of trazodone was safe and efficacious and may be used to facilitate confinement and enhance behavioral calmness of dogs during the critical recovery period following orthopedic surgery.

Acquisition of a visual discrimination and reversal learning task by Labrador retrievers.

Optimal cognitive ability is likely important for military working dogs (MWD) trained to detect explosives. An assessment of a dog's ability to rapidly learn discriminations might be useful in the MWD selection process. In this study, visual discrimination and reversal tasks were used to assess cognitive performance in Labrador retrievers selected for an explosives detection program using a modified version of the Toronto General Testing Apparatus (TGTA), a system developed for assessing performance in a battery of neuropsychological tests in canines. The results of the current study revealed that, as previously found with beagles tested using the TGTA, Labrador retrievers (N = 16) readily acquired both tasks and learned the discrimination task significantly faster than the reversal task. The present study confirmed that the modified TGTA system is suitable for cognitive evaluations in Labrador retriever MWDs and can be used to further explore effects of sex, phenotype, age, and other factors in relation to canine cognition and learning, and may provide an additional screening tool for MWD selection.

Conditioning laboratory cats to handling and transport.

As research subjects, cats have contributed substantially to our understanding of biological systems, from the development of mammalian visual pathways to the pathophysiology of feline immunodeficiency virus as a model for human immunodeficiency virus. Few studies have evaluated humane methods for managing cats in laboratory animal facilities, however, in order to reduce fear responses and improve their welfare. The authors describe a behavioral protocol used in their laboratory to condition cats to handling and transport. Such behavioral conditioning benefits the welfare of the cats, the safety of animal technicians and the quality of feline research data.

The use of a T-maze to measure cognitive-motor function in cats (Felis catus).

Few tests have been developed to test the cognitive and motor capabilities of domestic cats, in spite of the suitability of cats for specific studies of neuroanatomy, infectious diseases, development, aging, and behavior. The present study evaluated a T-maze apparatus as a sensitive and reliable measure of cognition and motor function of cats. Eighteen purpose-bred, specific-pathogen-free, male, neutered domestic shorthair cats (Felis catus), 1-2 years of age, were trained and tested to a T-maze protocol using food rewards. The test protocol consisted of positional discrimination training (left arm or right arm) to criterion followed by two discrimination reversal tests. The two reversal tests documented the ability of the subjects to respond to a new reward location, and switch arms of the T-maze. Data were collected on side preference, number of correct responses, and latency of responses by the subjects. Aided by a customized computer program (CanCog Technologies), data were recorded electronically as each cat progressed from the start box to the reward arm. The protocol facilitated rapid training to a high and consistent level of performance during the discrimination training. This learning was associated with a decrease in the latency to traverse the maze to a mean of 4.80 ± 0.87 s indicating strong motivation and consistent performance. When the rewarded side was reversed in the test phase, cats required more trials to reach criterion, as expected, but again showed reliable learning. The latency to reward in the first session of reversal increased 86% from the first to the last trial indicating that it may provide a useful index of cognitive processing. Latencies subsequently decreased as the new reversal paradigm was learned. This paradigm provides a relatively rapid and reliable test of cognitive motor performance that can be used in various settings for evaluation of feline cognitive and motor function.

Posture estimation for a canine machine interface based training system.

Dogs and humans have worked in partnership throughout history thanks to dogs' unique capability of detecting signals in human voices or gestures and learning from human inputs. Traditional canine training methods rely solely on subjective visual observations made by trainers. We propose a canine body-area-network (cBAN) to incorporate context-aware sensing with objective detection algorithms to augment the sensitivity and specificity of human trainer's awareness of the dogs they are training. As an initial effort, we developed a Bluetooth-based wireless infrastructure and tested inertial measurement units as cBAN sensor nodes to electronically assess the posture of the dogs. As a result, we were able to optimize the sensor locations and distinguish different postures using the distinct patterns in the measured angles.

Use of trazodone as an adjunctive agent in the treatment of canine anxiety disorders: 56 cases (1995-2007).

OBJECTIVE: To evaluate efficacy of trazodone hydrochloride as an adjunctive treatment for anxiety disorders as well as treatment protocol, dose range, concurrent drug use, adverse events, and therapeutic response in dogs unresponsive to other pharmacologic agents. DESIGN: Retrospective case series. ANIMALS: 56 dogs with anxiety disorders treated at a referral veterinary behavior clinic. PROCEDURES: Medical records of dogs with anxiety disorders adjunctively treated with trazodone were retrospectively evaluated with respect to signalment, primary and secondary behavioral diagnoses, physical examination results, hematologic data (CBC and serum biochemical panel), pharmacologic management, and outcome. RESULTS: Overall, trazodone, used as an adjunctive agent in combination with other behavioral drugs, was well tolerated over a wide dose range and enhanced behavioral calming when administered on a daily or as-needed basis. CONCLUSIONS AND CLINICAL RELEVANCE: Although further controlled studies of dose range, efficacy, and safety are needed, trazodone may provide an additional therapeutic option for use in dogs that are unresponsive to conventional treatment.