Preferential blockade by clozapine of hyperlocomotion induced by non-competitive NMDA antagonist MK-801

Effect of clozapine on MK-801-induced hyperlocomotion and stereotypy as well as open field behavior was studied. Clozapine (0.1-7.5 mg/kg) dose-dependently blocked MK-801(0.5 mg/kg)-induced stereotypy. Both total and ambulatory responses were blocked by even the lower doses (0.1-0.5 mg/kg) of clozapine. In open field test, clozapine selectively blocked hyperambulation induced by MK-801 (0.1 mg/kg) whereas it potentiated MK-801 (0.1 mg/kg)-induced stereotypy at all the doses used. Haloperidol (0.25 and 0.5 mg/kg) and SCH 23390 (0.5 and 1 mg/kg) showed a dose-dependent effect on MK-801-induced behaviors while sulpiride (25 and 50 mg/kg) failed to modify MK-801-induced open field behavior. This study supports the preferential effect of clozapine on dopamine receptors located in mesolimbic area and further suggests the possibility of using open field behavior induced by MK-801 as a model for studying atypical antipsychotics.