Interaction between NMDA and CB2 function in the dorsal hippocampus on memory consolidation impairment: an isobologram analysis.

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 μg/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.