Possible interaction between the ventral hippocampal cannabinoid CB2 and muscarinic acetylcholine receptors on the modulation of memory consolidation in mice.

To clarify possible interaction between the ventral hippocampal cannabinoid CB2 receptors and the cholinergic system in control of the memory process, the effects of cannabinoid and acetylcholine receptor agents on memory consolidation have been investigated in mice. Animals implanted with bilateral cannulas at the CA3 region of the ventral hippocampus and microinjected with scopolamine and cannabinergic agents. These animals were tested using a one-trial step-down inhibitory avoidance task. The results indicated impairment of memory consolidation by posttraining intra-CA3 microinjection of scopolamine (1 and 2 µg/mouse). Nevertheless, coinjection of various doses of scopolamine (0.01, 1 and 2 µg/mouse) with an ineffective dose of AM630 (1 µg/mouse) or GP1a (1 µg/mouse) did not show any significant effect on deficiency of memory consolidation produced by scopolamine. Posttraining application of cannabinoid CB2 receptor antagonist, AM630 (1, 10 and 100 µg/mouse; intra-CA3) alone had no significant influence on memory performance, but its coinjection with significant dose of scopolamine (1 µg/mouse) decreased memory consolidation. Moreover, posttraining injection of GP1a, cannabinoid CB2 receptor agonist, (10 and 100 µg/mouse; intra-CA3) decreased memory consolidation. Posttraining coadministration of diverse doses of GP1a (1, 10 and 100 µg/mouse; intra-CA3) with an effective dose of scopolamine (1 µg/mouse) meaningfully increased deficiency of memory consolidation produced by GP1a (100 µg/mouse). In addition, all drugs had no significant effect on locomotion. Consequently, these results propose that a probable interaction between the CA3 cannabinoid CB2 receptors and muscarinic acetylcholine receptors (mAChR) modulates memory consolidation process in mice.