Selective inhibition of mesolimbic dopamine release following chronic administration of clozapine: involvement of α1-noradrenergic receptors demonstrated by in vivo voltammetry

The release of dopamine (DA) in vivo was compared in the striatum and nucleus accumbens following chronic (21 day) administration of clozapine (CLOZ) and repeated coadministration of haloperidol (HAL) and the α₁-noradrenergic (NE) receptor antagonist prazosin. Treatment with HAL reduced basal DA release in both brain regions, whereas treatment with CLOZ decreased basal DA release only in the accumbens. Chronic coadministration of HAL and prazosin resulted in decreased DA release in accumbens but not striatum. These results suggest that the α₁-NE receptor blocking properties of CLOZ may, in part, mediate its differential actions on nigrostriatal and mesolimbic DA release, an effect which may in addition contribute to its paucity of extrapyramidal side effects.