"Classical" and "atypical" antipsychotic drugs: differential antagonism of amphetamine- and apomorphine-induced alterations of spontaneous neuronal activity in the neostriatum and nucleus accumbens

The ability of clozapine and haloperidol to antagonize the depression of firing rate produced by d-amphetamine and apomorphine in the neostriatum and nucleus accumbens was tested in immobilized, locally anesthetized rats. In the neostriatum, an intraperitoneal injection of 2.5 mg/kg d-amphetamine or 1.0 mg/kg apomorphine produced a prolonged inhibition of neuronal activity that was reversed by a subjsequent injection of either 20 mg/kg clozapine or 2.0 mg/kg haloperidol. An analysis of the onset and magnitude of the blockade revealed that clozapine was more effective than haloperidol in reversing the amphetamine response but that both antipsychotic drugs produced a comparable blockade of the apomorphine-induced depression. Similar results were obtained in the nucleus accumbens. The data indicate that although clozapine acts equieffectively in the neostriatum and nucleus accumbens, this atypical antipsychotic drug, aside from blocking postsynaptic dopamine receptors, may exert at least some of its effects by preventing dopamine release.