Dopamine neurons projecting to the medial prefrontal cortex possess release-modulating autoreceptors.
The ability of dopamine (DA) agonists and antagonists to modulate the K+-evoked overflow of radioactivity from superfused slices of prefrontal cortex of the rat, preincubated with [3H]DA in the presence of 1 microM desipramine, was examined. Apomorphine and the putative autoreceptor-selective DA agonist EMD 23 448 inhibited the K+-evoked overflow of radioactivity, while the DA antagonist sulpiride enhanced the evoked overflow in a dose-dependent and stereoselective manner. The latter effect was partially reversed by EMD 23 448. More than 95% of the radioactivity retained by the slices chromatographed with DA, while deaminated metabolites represented the majority of both the basal efflux (84% metabolites, 4-5% DA) and evoked overflow (84% metabolites, 14% DA) of radioactivity. These findings indicate that mesoprefrontal DA neurons possess release-modulating nerve terminal autoreceptors. Previous studies have shown that these neurons lack synthesis-modulating autoreceptors. Thus, autoreceptors on prefrontal DA terminals appear to be coupled to regulation of the release but not the synthesis of DA.
Wolf
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Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Roth
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D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009627:Nomifensine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology
D007211:Indoles; D011954:Receptors, Dopamine; D009627:Nomifensine; C037307:3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-1)-butyl)indole; D013469:Sulpiride; D011188:Potassium; D003891:Desipramine