Effects of 7-keto dehydroepiandrosterone on voluntary ethanol intake in male rats

Administration of dehydroepiandrosterone (DHEA), a neurosteroid that can negatively modulate the GABAA receptor, has been shown to decrease voluntary intake of ethanol in rats. In vivo, DHEA can be metabolized to a variety of metabolites, including 3β-acetoxyandrost-5-ene-7,17-dione (7-keto DHEA), a metabolite without the prohormonal effects of DHEA. This study compared the effectiveness of 7-keto DHEA with DHEA for reducing ethanol intake in the same group of rats. The subjects, previously trained to drink ethanol using a saccharin-fading procedure, had access to ethanol for 30 min daily and the amount consumed was recorded. Subjects were administered 10 and 56 mg/kg of DHEA or 7-keto DHEA intraperitoneally 15 min before drinking sessions. Subjects received each particular dose daily until one of two criteria was met, that is, either ethanol intake did not differ by more than 20% of the mean for 3 consecutive days or for a maximum of 8 days. Both 10 and 56 mg/kg of 7-keto DHEA significantly reduced the dose of ethanol consumed. Although 10 mg/kg of 7-keto DHEA produced decreases similar to those found with DHEA, the 56-mg/kg dose of 7-keto DHEA was significantly more effective at decreasing the dose of ethanol consumed than the same dose of DHEA. These results show that 7-keto DHEA is comparable with, or possibly more effective than, DHEA at decreasing ethanol consumption in rats, and that 7-keto DHEA is a compound deserving further investigation as a possible clinical treatment for alcohol abuse without the prohormonal effects of DHEA.