Influence of antipsychotics on presynaptic receptors modulating the release of dopamine in synaptosomes of the nucleus accumbens of rats.
The release of preloaded [3H]dopamine (DA) from superfused synaptosomes stimulated by 30 mM K+ was investigated in the nucleus accumbens of rats. Under conditions preventing the uptake of DA (presence of 40 microM cocaine) release of [3H]DA was inhibited by DA and apomorphine in a concentration-dependent manner (IC50s 0.65 and 0.3 microM, respectively). The maximal inhibitory effects of DA, as well as of apomorphine, were about 50% of the controls. The DA-induced inhibition was antagonized by antipsychotics completely; the rank order of antagonistic potencies was haloperidol greater than clozapine greater than sulpiride; methiothepine was ineffective. Furthermore, the K+-stimulated release of [3H]DA was inhibited by serotonin in a concentration-dependent manner (IC50 = 0.9 microM). This inhibitory effect was antagonized by methiothepine with a high efficiency, by clozapine and methysergide with moderate efficiencies; haloperidol and sulpiride were ineffective. The experimental system demonstrated appears to be suitable for characterizing the DA- and serotonin-antagonistic potencies of antipsychotics and other drugs on presynaptic autoreceptors as well as receptors modulating release of DA in the nucleus accumbens.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects*; D011188:Potassium / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012686:Septal Nuclei / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects
D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D011954:Receptors, Dopamine; D012702:Serotonin Antagonists; D012701:Serotonin; D001058:Apomorphine; D011188:Potassium; D004298:Dopamine