Possible significance of clozapine-induced increase in brain dopamine

Clozapine elevates the concentration of dopamine in the brains of mice injected with doses of 5-20 mg/kg while a 40 mg/kg dose has no effect. This biphasic change in dopamine content is seen in both the striatum and olfactory tubercle. The elevated dopamine concentration is dose-dependently antagonized by apomorphine, while a corresponding clozapine-induced reduction in norepinephrine concentrations is unaffected by apomorphine. These results suggest that part of the action of clozapine may be to reduce the release of dopamine.