Synergistic effect between D-AP5 and muscimol in the nucleus accumbens shell on memory consolidation deficit in adult male Wistar rats: An isobologram analysis

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The nucleus accumbens (NAc) glutamatergic and GABAergic systems are involved in memory processes. This study was investigated the involvement of NAc shell GABAergic system on D-AP5 induced memory consolidation deficit. The elevated plus-maze (EPM) test-retest paradigm was employed to assess memory in adult male Wistar rats. The results indicated that post-training intra-NAc shell injection of bicuculline (GABAA receptor antagonist) did not alter emotional memory consolidation. However, post-training intra-NAc shell microinjection of muscimol (GABAA receptor agonist, 0.1 μg/rat) and D-AP5 (a competitive NMDA receptor antagonist, 4 μg/rat) decreased emotional memory consolidation, suggesting the drugs induced amnesia. Moreover, a sub-threshold dose of muscimol (0.05 μg/rat) potentiated the D-AP5 (2 μg/rat) response on memory consolidation impairment. On the other hand, the middle dose of bicuculline (0.25 μg/rat) reversed memory impairment induced by D-AP5 at the higher dose. Interestingly, there is a synergistic effect between D-AP5 and muscimol on impairment of emotional memory consolidation. None of the above doses changed the locomotor activity. Our results suggest that the glutamatergic and GABAergic neurons of the NAc shell interact with each other for modulation of emotional memory consolidation.

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