Inhibition of 5α-Reduced Steroid Biosynthesis Impedes Acquisition of Ethanol Drinking in Male C57BL/6J Mice Alcoholism: Clinical and Experimental Research OnlineEarly Articles 19 June 2008
Allopregnanolone (ALLO) is a physiologically relevant neurosteroid modulator of GABAA receptors, and it exhibits a psychopharmacological profile that closely resembles the post-ingestive effects of ethanol. The 5α-reductase inhibitor finasteride (FIN), which inhibits biosynthesis of ALLO and structurally related neurosteroids, was previously demonstrated to reduce the maintenance of limited-access ethanol consumption.
The primary aim of the current work was to determine whether FIN would reduce the acquisition of drinking in ethanol-naïve mice.
FIN dose-dependently blocked the acquisition of 10E drinking and prevented the development of ethanol preference, thereby suggesting that the GABAergic neurosteroids may be important in the establishment of stable drinking patterns. FIN-elicited reductions in 10E intake were primarily attributable to selective and marked reductions in bout frequency, as no changes were observed in bout size, duration, or lick rates following FIN treatment. FIN-treated mice continued to exhibit attenuated ethanol consumption after 2 weeks post-treatment, despite a full recovery in brain ALLO levels. A second study confirmed the rightward and downward shift in the acquisition of ethanol intake following 7 daily FIN injections. While there were no significant group differences in brain ALLO levels following the seventh day of ethanol drinking, ALLO levels were decreased by 28% in the FIN-50 group.
Although the exact mechanism is unclear, FIN and other pharmacological interventions that modulate the GABAergic system may prove useful in curbing ethanol intake acquisition in at-risk individuals.
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