Effects of intrahippocampal cannabinoid receptor agonist and antagonist on radial maze and T-maze delayed alternation performance in rats

Brain cannabinoid receptors are abundantly distributed in the hippocampus, however their detailed role in learning and memory remains unclear. This study investigated the role of hippocampal cannabinoid receptors for performing two kinds of working memory tasks. In experiment 1, intrahippocampal infusion of cannabinoid receptor agonist WIN 55,212-2 (1-2 mug/side) dose-dependently disturbed radial maze performance in rats. In experiment 2, WIN 55,212-2 (2 mug/side) disturbed the performance of delayed alternation in a T-maze by increasing the errors and successive errors, and on the other hand, a cannabinoid receptor antagonist AM 281 (1 mug/side) did not have any significant effects. Disruptive effect of WIN 55,212-2 on the number of errors in delayed alternation was blocked by the pretreatment with intraperitoneal AM 281 (2 mg/kg). Results suggest that hippocampal cannabinoid receptors are involved in the performance of working memory tasks. A possible role of endogenous cannabinoid system in the hippocampus was discussed in terms of an inhibitory adjustment of behavior based on the outcome of animals' previous response.