Preferential activation of dopamine overflow in prefrontal cortex produced by chronic clozapine treatment.

The effect of chronic treatment with clozapine on extracellular dopamine levels in the rat striatum, nucleus accumbens and medial prefrontal cortex (mPFC) was examined using intracerebral microdialysis. Clozapine (20 mg/kg/day x 21 days in drinking water) increased basal dopamine release in the mPFC but had no effect in the striatum or nucleus accumbens. After chronic treatment, an acute dose of clozapine (20 mg/kg i.p.) produced large and long-lasting increases in extracellular dopamine in all three brain regions. The data suggest that chronic clozapine produces a sustained enhancement in dopaminergic tone in the mPFC.