MK-801 potentiates morphine-induced impairment of memory consolidation in mice: involvement of dopaminergic mechanisms

Abstract

The purpose of the present research was to study the interaction between the non-competitive NMDA receptor antagonist MK-801 and morphine in memory consolidation. The involvement of dopamine (DA) mechanisms in this interaction was also studied. Four sets of experiments were carried out with CD1 mice in a one-trial inhibitory avoidance task with post-training injections of drugs. In a first series of experiments post-training administration of morphine or of the non-competitive NMDA receptor antagonist MK-801 impaired memory consolidation. In the second set of experiments the memory consolidation impairment exerted by MK-801 was potentiated by the administration of the D₁ dopamine (DA) receptor antagonist SCH 23390 and by that of the D₂ DA receptor antagonist (−)-sulpiride. In the third set of experiments, administration of a dose of MK-801 ineffective by itself potentiated the memory impairment exerted by morphine. In the fourth series of experiments, similar ineffective doses of the D₁ DA receptor agonist SKF 38393 or of the D₂ DA receptor agonist LY 171555 antagonized the impairment of memory consolidation produced by MK-801 and morphine in combination, suggesting the involvement of dopaminergic mechanisms.