Effects of neuroleptics on dopamine release from striatal slices.

The neuroleptics which have antidopaminergic effects also enhanced brain dopamine (DA) turnover (Carlsson, 1963). Following administration of neuroleptics, the levels of DA metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased in several brain regions (Westerick, 1978) and a reduction in striatal DA fluorescence intensity was found in rats pretreated with alpha-methyl-paratyrosine (Yoshida et al. 1981). The enhancement of DA turnover by neuroleptics seemed to be caused by positive feedback due to a DA receptor blocking action, however it is unknown whether the enhancement of DA turnover is due to feedback or a direct blockade of DA autoreceptors at sites on the DA nerve endings. Attempts were made to use a superf usion apparatus to clarify the mechanism of the enhancement of DA efflux by neuroleptics. In the present study, longitudinal changes of DA efflux caused by haloperidol (HPD) superf usion and drug potencies of HPD, chlorpromazine (CPZ) and sulpiride (SUL) in enhancing DA efflux were investigated.