The interaction of opiate, cholinergic, glutamatergic and (possibly) dopaminergic inputs in the nucleus accumbens (NAc) to influence a learned behavior is certainly a topic of great interest. In the present study, the possible involvement of N-methyl-D-aspartate (NMDA) receptors in the NAc in nicotine’s effect on impairment of memory by morphine was investigated. Passive avoidance task was used for memory assessment in male wistar rats. Subcutaneous (s.c.) administration of morphine (5 and 10 mg/kg) after training impaired memory performance in the animals when tested 24 h later. Pre-test administration of the same doses of morphine reversed impairment of memory due to post-training administration of the opioid. Moreover, administration of nicotine (0.2 and 0.4 mg/kg, s.c.) before the test prevented impairment of memory by morphine (5 mg/kg) given after training. Impairment of memory performance in the animals due to post-training administration of morphine (5 mg/kg), was also prevented by pre-test administration of a non-competitive NMDA receptor antagonist, MK-801 (0.75 and 1 µg/rat). Interestingly, an ineffective dose of MK-801 (0.5 µg/rat) in combination with low doses (0.075 and 0.1 mg/kg) of nicotine, which had no effects alone, synergistically improved memory performance impaired by morphine given after training. On the other hand, pre-test administration of NMDA (0.1 and 0.5 µg/rat) which had no effect alone, in combination with an effective dose (0.4 mg/kg, s.c.) of nicotine prevent the improving effect of nicotine on memory impaired by morphine given after training. The results suggest a possible role for NMDA receptors of the NAc in the improving effect of nicotine on the morphine-induced amnesia. The interaction of opiate, cholinergic, glutamatergic and (possibly) dopaminergic inputs in the nucleus accumbens (NAc) to influence a learned behavior is certainly a topic of great interest. In the present study, the possible involvement of N-methyl-D-aspa
