Abstract

RATIONALE: Convincing evidence has supported the pivotal role of N-methyl-D-aspartate receptors (NMDARs) and CB2Rs in the regulation of learning and memory. OBJECTIVE: In this study, the role of hippocampal (CA1 region) CB2 receptors on aversive memory consolidation deficit induced by D-AP5, a NMDA receptor antagonist, was evaluated. METHODS: Adult male Wistar rats received cannula implants that bilaterally targeted the CA1 region. Long-term memory was examined using the step-through type of passive avoidance task. RESULTS: Post-training, intra-CA1 microinjection of D-AP5 (0.5 and 0.75 mug/rat), GP1a (CB2 receptor agonist at dose of 150 ng/rat) and AM630 (CB2 receptor antagonist at doses 75 and 100 ng/rat) impaired memory consolidation processes. Intra-CA1 microinjection of a lower dose of GP1a or AM630 restored memory impairment induced by D-AP5 at the two higher doses, while AM630 decreased D-AP5 memory response at the lower dose. The isobologram analysis showed that there is a synergistic effect between D-AP5 and AM630 on memory consolidation deficit. CONCLUSIONS: These results suggest that CA1 CB2 receptors modulate memory consolidation impairment induced by D-AP5.