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Introduction: There is currently a debate over the interaction between Ca2+ channels and cannabinoid system on learning and memory processing. In this study, we examined the effect of acute injection of cannabinoid agonist (Win- 55212-2) (Win) or antagonist (AM251), following chronic injection of verapamil, as a L-type Ca2+ channels blocker, on passive avoidance (PA) test in male Wistar rats. Methods: Male Wistar rats weighing 200-250 g were used. The animals were randomly divided into two main groups. Firstly, these two groups were treated with i.p injection of verapamil (25 mg/kg) or saline for 13 days (once daily). Before PA training, each group was divided into three subgroups, which received verapamil (or saline), Win (1 mg/kg) or AM251 (1 mg/kg). Then, PA training (acquisition test) was performed and retrieval test was done 24 h after the training. Results: The results showed that Win as a cannabinoid receptor agonist and verapamil as an L-type Ca2+ channels blocker decreased the acquisition and retrieval of PA task, but AM251 as a cannabinoid antagonist improved PA task. Meanwhile, acute use of an antagonist, simultaneous with verapamil, prevent verapamil induced PA impairment effect. Conclusion: The results of the present study indicate that acute injection of cannabinoid agonist and chronic injection of verapamil decrease memory in the PA task, whereas acute injection of cannabinoid antagonist has the opposite effect on memory. Furthermore, there is an interaction between functions of L-type Ca2+ channels and cannabinoid system on learning and memory.

Keywords: CB1 receptor, Win-55212-2, AM251, Verapamil, Memory

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