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Fletcher P.J.,Center for Addiction and Mental Health | Fletcher P.J.,University of Toronto | Sinyard J.,Center for Addiction and Mental Health | Higgins G.A.,CanCog Technologies | Higgins G.A.,University of Toronto
Pharmacology Biochemistry and Behavior | Year: 2010

Previous work showed that 5-HT2C receptor agonists reduce cocaine self-administration on a progressive ratio (PR) schedule of reinforcement, whereas a 5-HT2C receptor antagonist enhances responding for cocaine. The present experiments examined the effects of Ro60-0175 (5-HT2C agonist) and SB242084 (5-HT2C receptor antagonist) in rats on responding for food on a PR schedule; responding was also determined in mice lacking functional 5-HT2C receptors. In food-restricted rats, lever pressing reinforced by regular food pellets or sucrose pellets was reduced by Ro60-0175. This effect was blocked by SB242084, and was absent in mice lacking functional 5-HT2C receptors. A number of studies examined the effects of SB242084 on responding for food under a variety of conditions. These included manipulation of food type (regular pellets versus sucrose pellets), nutritional status of the animals (food restriction versus no restriction), and rate of progression of the increase in ratio requirements on the PR schedule. In all cases there was no evidence of enhanced responding for food by SB242084. Mice lacking functional 5-HT2C receptors did not differ from wildtype mice in responding for food in either food-restricted or non-restricted states. The effects of Ro60-0175 are consistent with its effects on food consumption and motivation to self-administer cocaine. Unlike their effects on cocaine self-administration, pharmacological blockade of 5-HT2C receptors, and genetic disruption of 5-HT2C receptor function do not alter the motivation to respond for food. Because the 5-HT2C receptor exerts a modulatory effect on dopamine function, the differential effects of reduced 5-HT2C receptor mediated transmission on responding for food versus cocaine may relate to a differential role of this neurotransmitter in mediating these two behaviours. © 2010 Elsevier Inc.


PubMed | University of Guelph, Vivocore and CanCog Technologies
Type: | Journal: Journal of feline medicine and surgery | Year: 2016

This study assessed the anxiolytic effectiveness of a test diet (Royal Canin Feline Calm diet) supplemented with L-tryptophan and alpha-casozepine.Subjects were 24 cats that were classified as mildly or markedly fearful based on the presence of a person in their home room. Three different protocols were used to assess anxiety: (1) evaluation of the response to a human in the cats home room (home room test); (2) analysis of the response to placement in an empty test room (open-field test) and; (3) analysis of the response to an unfamiliar human (human interaction test). All three protocols were first run at baseline, and the results were used to assign the animals to control and test diet groups that showed equivalent fear and anxiety. Both groups were retested on the three protocols after 2 weeks (test 1) and again after 4 weeks (test 2).The diet groups differed for two behavioral measures in the open-field test: inactivity duration and inactivity frequency. The control group showed statistically significant increases in inactivity duration between baseline and test 1 and baseline and test 2, while the group fed the test diet showed a marginally not significant decrease in inactivity duration between baseline and test 1 and a not significant decrease for test 2. There was also a significant increase in inactivity frequency between baseline and test 1 in the test diet group and marginally not significant decrease in the control group. There were no differences between groups in the approach of the cats toward people for the home room test and the human interaction test.These results suggest that the test diet reduced the anxiety response to placement in an unfamiliar location, but that fear in the presence of an unfamiliar person was not counteracted by the diet.


Collison K.S.,King Faisal Specialist Hospital And Research Center | Zaidi M.Z.,King Faisal Specialist Hospital And Research Center | Saleh S.M.,King Faisal Specialist Hospital And Research Center | Inglis A.,King Faisal Specialist Hospital And Research Center | And 6 more authors.
British Journal of Nutrition | Year: 2011

The incidence of obesity and type 2 diabetes mellitus (T2DM) is increasing, and new experimental models are required to investigate the diverse aspects of these polygenic diseases, which are intimately linked in terms of aetiology. Feline T2DM has been shown to closely resemble human T2DM in terms of its clinical, pathological and physiological features. Our aim was to develop a feline model of diet-induced weight gain, adiposity and metabolic deregulation, and to examine correlates of weight and body fat change, insulin homeostasis, lipid profile, adipokines and clinical chemistry, in order to study associations which may shed light on the mechanism of diet-induced metabolic dysregulation. We used a combination of partially hydrogenated vegetable shortening and high-fructose corn syrup to generate a high-fat-high-fructose diet. The effects of this diet were compared with an isoenergetic standard chow, either in the presence or absence of 1•125 % dietary monosodium glutamate (MSG). Dual-energy X-ray absorptiometry body imaging and a glucose tolerance test were performed. The present results indicate that dietary MSG increased weight gain and adiposity, and reduced insulin sensitivity (P < 0•05), whereas high-fat-high-fructose feeding resulted in elevated cortisol and markers of liver dysfunction (P < 0•01). The combination of all three dietary constituents resulted in lower insulin levels and elevated serum β-hydroxybutyrate and cortisol (P < 0•05). This combination also resulted in a lower first-phase insulin release during glucose tolerance testing (P < 0•001). In conclusion, markers of insulin deregulation and metabolic dysfunction associated with adiposity and T2DM can be induced by dietary factors in a feline model. © 2011 The Authors.


Pan Y.,Nestlé | Araujo J.A.,CanCog Technologies | Araujo J.A.,University of Toronto | Burrows J.,CanCog Technologies | And 6 more authors.
British Journal of Nutrition | Year: 2013

Cognitive dysfunction syndrome is a major disease affecting old cats and is the consequence of severe and irreversible loss of brain cells and brain atrophy. The present study focused on the hypothesis that the optimal strategy for promoting successful brain ageing is to target risk factors associated with brain ageing and dementia. We used a nutritional strategy involving supplementation with a blend of nutrients (antioxidants, arginine, B vitamins and fish oil) to test this hypothesis. Middle-aged and old cats between 5·5 and 8·7 years of age were assigned to cognitively equivalent control or treatment groups based on prior cognitive experience and performance on baseline cognitive tests. The cats in the treatment group were maintained on a diet supplemented with the nutrient blend and the cats in the control group were maintained on the identical base diet without the additional supplementation. After an initial wash-in period, all cats were tested on a battery of cognitive test protocols. The cats fed the test diet showed significantly better performance on three of four test protocols: a protocol assessing egocentric learning, a protocol assessing discrimination and reversal learning and a protocol focused on acquisition of a spatial memory task. The results support the hypothesis that brain function of middle-aged and old cats can be improved by the nutrient blend that was selected to minimise or eliminate the risk factors associated with brain ageing and dementia. © 2012 The Authors.


Pan Y.,Nestlé | Larson B.,Nestlé | Araujo J.A.,CanCog Technologies | Araujo J.A.,University of Toronto | And 7 more authors.
British Journal of Nutrition | Year: 2010

The present study focused on the hypothesis that dietary supplementation with medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing the brain with energy in the form of ketones. Aged Beagle dogs were subjected to a baseline battery of cognitive tests, which were used to establish cognitively equivalent control or treatment groups. The dogs in the treatment group were maintained on a diet supplemented with 5.5% MCT. After an initial wash-in period, all the dogs were tested with a battery of cognitive test protocols, which assessed sequentially landmark discrimination learning ability, egocentric visuospatial function and attention. The groups were maintained on the diets for 8 months. The MCT-supplemented group showed significantly better performance in most of the test protocols than the control group. The group differences also varied as a function of task difficulty, with the more difficult task showing greater supplementation effects than the easier tasks. The group given the MCT supplement showed significantly elevated levels of β-hydroxybutyrate, a ketone body. These results indicate, first, that long-term supplementation with MCT can have cognition-improving effects, and second, that MCT supplementation increases circulating levels of ketones. The results support the hypothesis that brain function of aged dogs can be improved by MCT supplementation, which provides the brain with an alternative energy source. © 2010 The Authors.


Zanghi B.M.,Nestlé | Araujo J.,CanCog Technologies | Milgram N.W.,CanCog Technologies
Animal Cognition | Year: 2015

Cognition in dogs, like in humans, is not a unitary process. Some functions, such as simple discrimination learning, are relatively insensitive to age; others, such as visuospatial learning can provide behavioral biomarkers of age. The present experiment sought to further establish the relationship between various cognitive domains, namely visuospatial memory, object discrimination learning (ODL), and selective attention (SA). In addition, we also set up a task to assess motor learning (ML). Thirty-six beagles (9–16 years) performed a variable delay non-matching to position (vDNMP) task using two objects with 20- and 90-s delay and were divided into three groups based on a combined score (HMP = 88–93 % accuracy [N = 12]; MMP = 79–86 % accuracy [N = 12]; LMP = 61–78 % accuracy [N = 12]). Variable object oddity task was used to measure ODL (correct or incorrect object) and SA (0–3 incorrect distractor objects with same [SA-same] or different [SA-diff] correct object as ODL). ML involved reaching various distances (0–15 cm). Age did not differ between memory groups (mean 11.6 years). ODL (ANOVA P = 0.43), or SA-same and SA-different (ANOVA P = 0.96), performance did not differ between the three vDNMP groups, although mean errors during ODL was numerically higher for LMP dogs. Errors increased (P < 0.001) for all dogs with increasing number of distractor objects during both SA tasks. vDNMP groups remained different (ANOVA P < 0.001) when re-tested with vDNMP task 42 days later. Maximum ML distance did not differ between vDNMP groups (ANOVA P = 0.96). Impaired short-term memory performance in aged dogs does not appear to predict performance of cognitive domains associated with object learning, SA, or maximum ML distance. © 2015, Springer-Verlag Berlin Heidelberg.


Zanghi B.M.,Nestlé | Gardner C.,Nestlé | Araujo J.,InterVivo Solutions | Milgram N.W.,CanCog Technologies
Neurobiology of Sleep and Circadian Rhythms | Year: 2016

Core body temperature (CBT) rhythm, locomotor activity, and actigraphy-sleep were evaluated in geriatric dogs with cognitive dysfunction. Dogs (n=33; 9–16 yrs) performed a spatial working memory task and divided into three memory groups: Low, Moderate, and High, with subsequent evaluation of learning and attention. Rectal CBT was recorded 6 times over a 17.5 h period and Actiwatch® activity monitoring system for 5 days while housed indoors with 12 h light/dark schedule. Rhythm of daily activity data was evaluated using the traditional cosinor analysis and generation of non-parametric measures of interdaily stability, intradaily variability, and relative amplitude. CBT differed with time (F (5, 130)=11.36, p<0.001), and was the highest at 19:00C. CBT at 19:00 was positively related (p<0.01) to memory (r(31)=0.50) and 3-domain cognitive performance index (memory, learning, attention; r(31)=0.39). Total daytime or night-time activity did not differ between memory groups, but hourly counts at 8:00 were positively related (p<0.05) to memory (r(31)=0.52), learning (r(31)=0.36), and 3-domain cognitive performance index (r(31)=0.53). There were no significant differences between age or memory groups for any circadian rhythm measures. Daytime naps were inversely related to memory accuracy (r(31)=−0.39; p<0.05) and BT at 15:00 (r(30)=−0.51; p<0.01). Lower peak BT and increased napping may predict some aspects of cognitive performance of working memory, learning, and/or attention processes in these geriatric dogs, but minimal diurnal rhythm disruption of locomotor activity is observed when these cognitive processes decline. © 2016 The Authors


PubMed | CanCog Technologies, Bowden Analytics and North Carolina State University
Type: Journal Article | Journal: Journal of veterinary behavior : clinical applications and research : official journal of : Australian Veterinary Behaviour Interest Group, International Working Dog Breeding Association | Year: 2015

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.


PubMed | CanCog Technologies, Animal Behaviour Consultations and Vivocore Inc
Type: | Journal: Journal of feline medicine and surgery | Year: 2016

The objectives of this study were: (1) to develop a laboratory-based model to assess fear and anxiety in cats using the feline open-field test (OFT) and the feline human interaction test (HIT); and (2) to validate the model using diazepam, a known anxiolytic.Laboratory-housed cats (n = 41) were first classified as fearful, mildly fearful or non-fearful by a technician familiar with the cats and also by veterinary behaviorists (GL, JL), by assessing the cats behavior in their home rooms. In experiment 1, each cats behavior was assessed in an OFT and an HIT. In experiment 2, after administration of the anxiolytic diazepam, a subset of the cats was re-tested.In experiment 1, the OFT revealed significant group effects on two measures: duration of inactivity, and vocalization. Fearful animals had significantly longer periods of inactivity than non-fearful animals. Non-fearful and mildly fearful cats vocalized more frequently than fearful cats. In the HIT, fearful cats travelled less than non-fearful and mildly fearful cats. Fearful and mildly fearful animals had significantly longer durations of inactivity, and non-fearful and mildly fearful cats had a significantly higher frequency of vocalization compared with fearful cats. In experiment 2, in the OFT, treatment with diazepam caused an increase in distance travelled, shorter durations of inactivity, and more frequent inactivity and vocalization. In the HIT, diazepam increased distance travelled and decreased duration of inactivity. Fearful cats spent significantly less time near the human compared with non-fearful cats, and this persisted under diazepam.The feline OFT and feline HIT can be used jointly to assess the effects of medications or other therapies on fear and anxiety in the domestic cat.


PubMed | InterVivo Solutions, 99 Technologies, CanCog Technologies, MDStat Consulting and Ceva Sante Animale
Type: Controlled Clinical Trial | Journal: The Veterinary record | Year: 2015

The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs nave to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across during and post thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity.

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