Chronic haloperidol decreases dopamine release in striatum and nucleus accumbens in vivo: depolarization block as a possible mechanism of action.

The effects of chronic haloperidol administration on the basal release of endogenous dopamine (DA) in the intact rat striatum and nucleus accumbens were investigated using in vivo electrochemical techniques. Repeated (21 day) treatment with haloperidol produced marked decreases in the release of DA in both brain regions. Administration of apomorphine to vehicle-treated control animals rapidly reduced DA release, in accord with its inhibitory, hyperpolarizing actions on DA neurons. In contrast, apomorphine reversed the haloperidol-induced reductions in DA release to values that were not significantly different from those measured in control animals. The present study is the first report to demonstrate decreased DA release in response to chronic neuroleptic treatment and to present evidence for induction of depolarization block of DA cell firing as a possible mechanism underlying this effect.