Background: The interaction of opiate, cholinergic, glutamatergic and (possibly) dopaminergic inputs in the ventral tegmental area (VTA) to influence a learned behavior is certainly a topic of great interest. In the present study, the effect of N-methyl-D-aspartate (NMDA) receptors in the VTA in nicotine’s effect on improvement of state-dependent memory of morphine was investigated. Methods: A step-through inhibitory avoidance (IA) task was used for memory assessment in male Wistar rats. Results: Subcutaneous (s.c.) administration of morphine (5 and 7.5 mg/kg) after training impaired IA memory. Pre-test administration of the same doses of morphine and nicotine (0.2, 0.4 and 0.6 mg/kg, s.c.), 30 min before the test, reversed the memory impairment. Blockade of NMDA receptors by intra-VTA administration of their competitive antagonist, D-AP5 (0.25, 0.5, 1 and 2 µg/rat) alone had no effect on memory impairment induced by morphine. On the other hand, intra-VTA administration of D-AP5 (0.5, 1 and 2 µg/rat) in combination with an effective dose of nicotine (0.4 mg/kg, s.c.) prevented the improving effect of nicotine on state-dependent memory of morphine. Conclusions: It can be concluded that NMDA receptors in the VTA may modulate the effect of nicotine on memory.
