Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum
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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 μM) 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 μM haloperidol on 3H-DA release could be blocked by 10 μM cocaine, but not with 1 μM 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.
Key wordsDA-release Neuroleptics Striatum slices GABA release Presynaptic DA receptors
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