Regulation of the prefrontal cortical dopamine system by the neuroactive steroid 3a,21-dihydroxy-5a-pregnane-20-one.

Grobin AC, Roth RH, Deutch AY
Brain Res. 1992 578 (1-2): 351-6

PMID: 1511287 · DOI:10.1016/0006-8993(92)90270-j

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.

MeSH Terms (17)

3,4-Dihydroxyphenylacetic Acid Anesthetics Animals Cerebral Cortex Cerebral Ventricles Desoxycorticosterone Dopamine Dose-Response Relationship, Drug Exploratory Behavior Homovanillic Acid Injections, Intraventricular Male Motor Activity Rats Rats, Inbred Strains Reference Values Stress, Psychological

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