title: Influence of antipsychotics and serotonin antagonists on presynaptic receptors modulating the release of serotonin in synaptosomes of the nucleus accumbens of rats.
abstract: In the nucleus accumbens of rats the release of [3H]serotonin (5-HT) from superfused synaptosomes stimulated by 30 mM K+ was investigated. In the presence of 40 microM of the uptake inhibitor cocaine the release of [3H]5-HT was inhibited by 5-HT in a concentration-dependent manner (IC50 = 0.45 microM). The maximum inhibitory effect of 5-HT was 54% of controls. The inhibition of K+-stimulated release of [3H]5-HT induced by 5-HT was antagonized completely by methiothepine and clozapine, respectively, whereas methysergide had only a weak antagonizing effect in a concentration of 20 microM or less, haloperidol was ineffective. Furthermore, the synaptosomal K+-stimulated release of [3H]5-HT was also inhibited by dopamine (DA) in a concentration-dependent manner (IC50 = 0.1 microM). This inhibitory effect was antagonized by antipsychotic drugs, the rank order of antagonistic potencies was sulpiride greater than haloperidol greater than clozapine; methiothepine was ineffective. The experimental system (the K+-stimulated synaptosomal release of [3H]5-HT seems to be a suitable model for differentiating dopaminergic and/or serotonergic components of antipsychotics or other drugs on presynaptic receptors.
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D066298:In Vitro Techniques; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012686:Septal Nuclei / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D004298:Dopamine