| Abstract No.: | C-G3187 |
| Country: | Canada |
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| Title: | FACILITATION OF SOCIAL RECOGNITION BY INCREASED ACTIVATION OF THE CANNABINOID SYSTEM USING URB597 |
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| Authors/Affiliations: | 1 Darryl Bannon*; 1 Cheryl Limebeer; 1 Elena Choleris;
1 University of Guelph, ON, Canada.
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| Content: | Objectives: Cannabis is often used as a recreational drug in social settings and as such its social implications are of interest. One method for examining the social effects is to investigate the effects of pharmacological manipulations in rodent models of social behaviour. One means of cannabinoid regulation is intracellular hydrolysis using fatty-acid amide hydrolase (FAAH). URB597 is a drug that inhibits FAAH thereby causing an increase in cannabinoid concentrations in active synapses. This study is intended to examine whether increasing active synapse cannabinoids will facilitate social investigation of a novel conspecific in a social recognition paradigm, and whether it will do so in a dose-dependent manner.
Materials and Methods: The social recognition paradigm used involved a CD1 intact male mouse presented with two conspecific castrated stimulus mice in its home cage. The intruder mice were placed in the home cage so that the experimental mouse could smell but not touch the intruders. The experimental mouse was habituated to the stimulus mice over 4 presentations. After the fourth presentation there was a dishabituation trial in which one of the two intruder mice was replaced with a novel conspecific. The experimental mouse was either uninjected or given a 0.1 mg/kg IP injection of a vehicle (2-hydroxypropyl-beta-cyclodextrin) or 0.05, 0.1 or 0.4 mg/kg URB597 1 hour prior to the test. Social interaction was defined as directly sniffing at the holes of the cylinder containing a stimulus mouse.
Results: The experimental mice in the 0.1 mg/kg were the only group to show a significant increase (p<.01) in the % time they spent investigating the novel stimulus mouse relative to the familiar stimulus mouse from trial 4 to trial 5. This indicates social recognition in the 0.1 dose. The experimental mice in the 0.1 mg/kg URB597 group had the highest % exploration of the novel stimulus at 80.3%. This preference for the novel stimulus mouse was significantly higher (p<.05) than the uninjected (63.1%; p<.05), vehicle (64.0%; p<.05), 0.05mg/kg (64.5%; p<.05) and 0.4 (58%; p<.01) groups.
Conclusions: The results suggest a curvilinear dose-response facilitation effect of URB597 on social recognition in mice suggesting that an increase in endogenous cannabinoid levels at active synapses may foster social behaviour. Overall, our results suggest that URB597 could have a beneficial role in the clinical treatment of social disorders in humans.
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