The influence of NMDA receptor agonist and antagonist on morphine state-dependent memory of passive avoidance in mice

The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To explore the possible involvement of NMDA modulators on morphine-induced memory impairment, we have investigated the effects of intracerebroventricular (i.c.v.) administration of NMDA and the competitive NMDA antagonist, dl-AP5, on morphine-induced memory impairment or recall, on the test day. Morphine (5 mg/kg, s.c.) was administered 30 min before training to induce impairment of memory and 24 h later, 30 min before test to improve it. Pre-test administration of NMDA (0.00001, 0.0001 and 0.001 μg/mouse, i.c.v.) did not alter the retention latency compared to the saline-treated animals. But restored the memory impairment induced by pre-training morphine (5 mg/kg, s.c.). Pre-test administration of dl-AP5 (1, 3.2 and 10 μg/mouse, i.c.v.) by itself decreased the retention latencies. The same doses of dl-AP5 increased pre-training morphine-induced memory impairment. Co-administration of NMDA (0.0001 and 0.001 μg/mouse, i.c.v.) and morphine (5 mg/kg, s.c.) on the test day increased morphine memory improvement. Conversely, dl-AP5 (1, 3.2 and 10 μg/mouse, i.c.v.) inhibited morphine-induced memory recall. It is concluded that NMDA receptors may be involved, at least in part, in morphine state-dependent learning in mice.