MODULATION OF MK-801 RESPONSE BY DOPAMINERGIC AGENTS IN MICE

Various doses of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801 (0.1-0.5 mg/kg) and ketamine (2.5-10 mg/kg), produced a dose-dependent increase in stereotypic behaviour in naive mice. MK-801 (0.1 mg/kg) and ketamine (2.5 mg/kg) potentiated the stereotypic response of apomorphine (0.1-0.5 mg/kg) in mice pretreated with reserpine (5 mg/kg, 24 h prior) and alpha-methyl-p-tyrosine (150 mg/kg, 1 h prior) but not in naive mice. SKF 38393, a D1 dopamine agonist, enhanced whereas B-HT 920, a D2 dopamine agonist, reduced the stereotypic response of MK-801 in naive mice. The response of MK-801 was blocked by pretreatment with haloperidol (0.5 mg/kg), molindone (2.5 mg/kg), clozapine (7.5 mg/kg) and SCH 23390 (0.1 mg/kg). The present data suggest involvement of endogenous DA transmission in the stimulant action of non-competitive NMDA antagonists in mice. Dopamine D1 and D2 receptor stimulation, respectively, exert opposing effects on the behavioural expression of MK-801 in mice.