Differential endocannabinoid regulation of extinction in appetitive and aversive Barnes maze tasks

CB1 receptor-compromised animals show profound deficits in extinguishing learned behavior from aversive conditioning tasks, but display normal extinction learning in appetitive operant tasks. However, it is difficult to discern whether the differential involvement of the endogenous cannabinoid system on extinction results from the hedonics or the required responses associated with the disparate tasks. Here, we report that the CB1 receptor antagonist rimonabant disrupts extinction learning in an aversive, but not in an appetitive, Barnes maze conditioning task. Accordingly, these results provide compelling support for the hypothesis that the endogenous cannabinoid system plays a necessary role in the extinction of aversively motivated behaviors but is expendable for appetitively motivated behaviors. The centrally occurring endogenous cannabinoid (endocannabi-noid) system is comprised of the G-protein-coupled CB1 receptor, its endogenous ligands, 2-arachyldonyl glycerol (2-AG) and an-andamide (AEA), and enzymes responsible for the biosynthesis and degradation of these ligands (Ahn et al. 2008). A growing body of literature has implicated the endocannabinoid system in extinction learning in which learned behavior becomes sup