Introduction: In the present study, the effects of intracerebroventricular (i.c.v.) injection of N-methyl-D-aspartate (NMDA) receptor agonists and competitive or noncompetitive antagonists, on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice.
Methods: Each mouse was anaesthetized and its head was oriented in a stereotaxic instrument. A stainless-steel cannula was positioned above the right lateral cerebral ventricle. We tested the hypothesis in a well-established state-dependent learning (two by-two factorial design), and step-down passive avoidance method.
Results: 1) 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. 2) Pre-test administration of L-glutamate (10-3, 10-4, 10-5 g/mouse, i.c.v.) and NMDA (10-3, 10-4, 10-5 g/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.). 3) Pre-test administration of DL-AP5 (1, 3.2 and 10 µg/mouse, i.c.v.) and MK-801 (0.5, 1 and 2 g/mouse, i.c.v.), by itself decreased the retention latencies. The same doses of DL-AP5 and MK-801 increased pre-training morphine-induced memory impairment. 4) Co-administration of L-glutamate (10-3, 10-4, 10-5 g/mouse, i.c.v.) and/or NMDA (10-3, 10-4, 10-5 g/mouse, i.c.v.) and morphine (5 mg/kg, s.c.) on the test day, increased morphine memory improvement. 5) Co-administration of DL-AP5 (1, 3.2 and 10 µg/mouse, i.c.v.) and MK-801 (0.5, 1 and 2 g/mouse, i.c.v.) inhibited morphine-induced memory recall.
Conclusion: The results suggest that NMDA receptors are involved in morphine state-dependent learning in mice.