Glutamate and dopamine neurotransmitter systems, particularly glutamate N-methyl-D-aspartate (NMDA) and dopamine D-1 receptors, appear to play a key integrative role in motivation, learning and memory. The nucleus accumbens (NAc) is also involved in reward, motivation, movement, learning and memory. GABAergic mdium spiny projection neurons of NAc receive dopaminergic afferent innervations from ventral tegmental area and glutamatergic afferents from the cerebral cortex, thalamus, hippocampus and amygdala. A common feature of many addictive drugs, including nicotine, is that they increase dopamine levels in the NAc which ultimately leads to reward-related memory. Considering the distribution of NMDA receptors in the NAc, in the present study, the role of NMDA receptors on the NAc neurons in the effects of nicotine on memory was evaluated. To assess memory performance of male wistar rats, step-through inhibitory avoidance task was selected. Post-training injection of morphine (5 and 10 mg/kg, s.c.) impaired memory performance. Twenty four hours later, not only administration of the same doses of morphine but also nicotine (0.2 and 0.4 mg/kg, s.c.), 30 min prior to testing, restored performance. Intra-NAc administration of different doses (0.0001, 0.001, 0.01, 0.1 and 0.5 µg/rat) of NMDA receptor agonist alone, 5 min before testing, had no effect on performance impaired by morphine. In the other hand, intra-NAc injection of MK801, an NMDA receptor antagonist (0.75 and 1 µg/rat) alone, 5 min before testing, restored performance impaired by morphine. An ineffective dose (0.5 µg/rat) of MK801 increased the effect of sub-effective doses (0.05, 0.075 and 0.1 mg/kg, s.c.) of nicotine. It can be concluded that NMDA receptors in the NAc may be modulate the effect of nicotine on memory.
