Clozapine potently stimulates mesocortical dopamine neurons.

The effects of clozapine on dopamine neurons projecting to the medial-prefrontal cortex, nuclei accumbens and caudatus were compared. Clozapine (1.25 mg/kg i.v.) maximally stimulated the firing rate and burst activity of dopamine neurons projecting to the medialprefrontal cortex. Much higher doses (5 and 10 mg/kg i.v.) were needed to stimulate mesoaccumbens and nigrostriatal dopamine neurons. The results suggest that the activation of mesocortical dopamine neurons is responsible for clozapine-induced dopamine release in the prefrontal cortex.