Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum

Summary The characteristics of ³H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1–1 M) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect.The butyrophenones strongly inhibited the electrically stimulated overflow of both ³H-DA and ¹⁴C-GABA, while the phenothiazines again had little effect. The action of 1 M haloperidol on ³H-DA release could be blocked by 10 M cocaine, but not with 1 M apomorphine. Apomorphine itself had no significant effect on ³H-DA release.Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up ³H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS.