Involvement of NMDA receptors in morphine state-dependent learning in mice

In the present study, the effects of intracerebroventricular (i.c.v.) injection of NMDA receptor agonist and antagonist on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pretraining administration of morphine (5 mg/kg; s.c.) decreased the learning of one-trial passive avoidance task. Pretest administration of morphine (5 mg/kg) induced state-dependent learning acquired under pretraining morphine influence. Pretest administration of NMDA receptor agonist, L-glutamate (0.00001 and 0.0001 and 0.001 microg/mouse, i.c.v.) following pretraining saline treatment did not affect retention. Amnesia induced by pretraining morphine was significantly reversed by pretest administration of L-glutamate (0.0001 and 0.001 microg/mouse, i.c.v.). Pretest administration of noncompetitive NMDA receptor antagonist, MK-801 (0.5, 1, and 2 microg/mouse, i.c.v.) significantly impaired memory formation. Amnesia induced by pretraining morphine was increased by pretest administration of MK-801 (2 microg/mouse, i.c.v.). Pretest coadministration of L-glutamate (0.0001 and 0.001 microg/mouse, i.c.v.) or MK-801 (0.5, 1, and 2 microg/mouse, i.c.v.) with morphine (5 mg/kg, s.c.) increased and decreased morphine state-dependent learning, respectively. The results suggest that NMDA receptors are involved in morphine state-dependent learning in mice.