Dorsal hippocampal cannabinergic and GABAergic systems modulate memory consolidation in passive avoidance task

Abstract

In the present research, we examined the possible interaction between the hippocampal CB2 and GABAA receptors on modulation of memory consolidation. In this research, step-down passive a .voidance task was used to evaluate memory consolidation in adult male NMRI mice. The results showed that post-training intra-CA1 administration of muscimol (0.05 and 0.1 μg/mouse) impaired memory consolidation as evidenced by a decrease in step-down latency on the test day, which was suggestive of drug-produced amnesia. However co-administration of different doses of muscimol (0.01, 0.05 and 0.1 μg/mouse) along with a not-effect dose of AM630 (1 μg/mouse) or GP1a (1 μg/mouse) had no significant effect on impairment of memory consolidation induced by muscimol. Although post-training intra-CA1 administration of the cannabinoid CB2 receptor antagonist, AM630 (1, 10 and 100 μg/mouse) alone had no effect, its co-administration with an effective dose of muscimol (0.05 μg/mouse) impaired memory consolidation. Furthermore, post-training intra-CA1 microinjection of cannabinoid CB2 receptor agonist, GP1a (100 μg/mouse) impaired memory consolidation. Interestingly, post-training intra-CA1 co-injection of different doses of GP1a (1, 10 and 100 μg/mouse) along with an effect dose of muscimol (0.05 μg/mouse) significantly intensified impairment of memory consolidation induced by GP1a (10 μg/mouse). Moreover, all above doses of drugs did not significantly change locomotor activity. These findings suggest possible interaction between the CA1 cannabinoid CB2 and GABAA mechanisms on modulation of memory consolidation in mice.