Chronic treatment with classical and atypical antipsychotic drugs differentially decreases dopamine release in striatum and nucleus accumbens in vivo.

In vivo electrochemical techniques were employed to demonstrate that repeated treatment with classical antipsychotic drugs reduced basal dopamine (DA) release in the striatum and nucleus accumbens, whereas repeated treatment with atypical antipsychotics decreased DA release only in accumbens. Administration of apomorphine temporarily reversed these decreases to values comparable to those measured in vehicle-treated controls. These results suggest that the delayed onset of antipsychotic efficacy and extrapyramidal side effects involve a decrease in DA release in mesolimbic and nigrostriatal DA terminal fields, respectively. The results further suggest that induction of depolarization block in DA neurons may be the mechanism underlying these effects.