Strain-dependent interactions between MK-801 and cocaine on retention of C57BL/6 and DBA/2 mice tested in a one-trial inhibitory avoidance task: Involvement of dopaminergic mechanisms

Two sets of experiments were carried out with C57BL/6 (C57) and DBA/2 (DBA) mice tested in a one-trial inhibitory avoidance task. In the first set C57 and DBA mice were injected posttraining with saline or with the D1 DB rece ptor antagonist SCH 23390 and then with saline, cocaine (5 mg/kg), MK-801 ( 0.1 mg/kg), or with a combination of these two drugs. Cocaine enhanced rete ntion in the C57 strain and impaired it in the DBA strain, and MK-801 poten tiated the effects of cocaine in both strains. Furthermore, pretreatment wi th SCH 23390 completely antagonized the potentiation of the effects of coca ine exerted by MK-801. In the second set of experiments mice belonging to t hese same two strains were injected posttraining with vehicle or with the D 2 DA receptor antagonist (-)-sulpiride and then with saline, cocaine (5 mg/ kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Pretreat ment with the D2 DA receptor antagonist completely antagonized in both stra ins the potentiation of the effect of cocaine exerted by MK-801. The result s of the present research show that the noncompetitive NMDA receptor antago nist MK-801 enhances the effect of cocaine on retention performance in C57 and DBA mice and that dopaminergic mechanisms are involved in this potentia tion. (C) 2000 Academic Press.