Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum.
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 micronM) 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 micronM haloperidol on 3H-DA release could be blocked by 10 micronM cocaine, but not with 1 micronM 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.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D005476:Fluphenazine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D013134:Spiperone / Q000494:pharmacology
D014150:Antipsychotic Agents; D013134:Spiperone; D003042:Cocaine; D006220:Haloperidol; D001058:Apomorphine; D005476:Fluphenazine; D002746:Chlorpromazine; D004298:Dopamine