Apomorphine does not reverse reduced basal dopamine release in rat striatum and nucleus accumbens after chronic haloperidol treatment.

Chronic administration of haloperidol (2 mg/kg x 21 days) in drinking water decreased basal dopamine (DA) release and metabolism in rat striatum and nucleus accumbens in awake, freely moving rats. In contrast with previous in vivo voltammetric studies in chloral hydrate-anesthetized rats, DA release and metabolism decreased in both regions following administration of (-)apomorphine (50 micrograms/kg, i.v.). These results demonstrate that stimulation of pre- or postsynaptic DA receptors by apomorphine in rats chronically treated with haloperidol further diminishes the release of DA and decreases DA metabolism. These results are difficult to reconcile with current concepts of neuroleptic-induced depolarization inactivation which predict increased release of DA following DA agonist administration.