Regulation of the prefrontal cortical dopamine system by the neuroactive steroid 3a,21-dihydroxy-5a-pregnane-20-one.
The dopamine innervation of the prefrontal cortex can be differentiated from other telencephalic dopamine projection fields by its sensitivity to stress. The stress-induced activation of the mesoprefrontal cortical dopamine system can be blocked by pretreatment with benzodiazepines. A group of neuroactive steroids that modulate GABA-induced chloride flux through means distinct from that of the benzodiazepines has recently been identified. Intraventricular administration of the neuroactive steroid 3 alpha,21-dihydroxy-5 alpha-pregnane-20-one resulted in a dose-dependent decrease in dopamine metabolites in the prefrontal cortex, but not in mesolimbic or striatal sites; sedative effects were not observed. Moreover, the neuroactive steroid selectively attenuated the stress-induced activation of the mesoprefrontal cortical dopamine system. These data suggest that neuroactive steroids may function as endogenous anxiolytic agents.
Grobin
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AC
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Roth
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Deutch
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013315:Stress, Psychological / Q000503:physiopathology
D000777:Anesthetics; D015102:3,4-Dihydroxyphenylacetic Acid; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D004298:Dopamine; D006719:Homovanillic Acid