Clozapine an atypical neuroleptic does not affect dopamine (DA) neuronal function in the same manner as typical neuroleptics, which may explain why it produces relatively few extrapyramidal side effects. To gain better insight into how these two classes of neuroleptics influence central DA metabolism, we compared DA turnover and release following acute and chronic doses of clozapine and haloperidol. DA turnover was assessed from changes in the concentration of the DA metabolites 3.4- dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). DA release was assessed from the rate of accumulation of 3-methoxy-tyramine (3MT) after administration of a high dose of pargyline, a potent monoamine oxidase inhibitor. Three brain regions were studied: the frontal cortex, the nucleus accumbens and the caudate nucleus. Prior reports of enhanced non-phasic subcortical dopamine release in rats chronically treated with neuroleptics, and the possibility that this type of dopamine release is similar to impulse independent dopamine release, led us to carry out a number of experiments that specifically address this issue. In our study, dopamine release was evaluated in rats chronically treated with neuroleptics 30 min. after the administration of the potent impulse flow blocker, gamma-butyrolactone.
