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 behavioral expression of MK-801 in mice.
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
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Kulkarni
D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007649:Ketamine; D016291:Dizocilpine Maleate; D012110:Reserpine