Assessment of pregnenolone effects on alcohol intake and preference in male alcohol preferring (P) rats

Neuroactive steroids can modulate a variety of neurobehavioral functions via the GABAergic system. This study was conducted to determine the importance of the neurosteroid pregnenolone on the regulation of alcohol intake. The effects of acute and chronic administration of pregnenolone on alcohol intake were assessed in alcohol preferring (P) rats. The rats were injected i.p. with the vehicle or pregnenolone (25, 50 or 75 mg/kg) and their alcohol and water intake were recorded at 2, 4, 6 and 24 h. Also, the chronic effects of 50 mg/kg (i.p.) pregnenolone on alcohol intake were determined. Our results show that although the main effect of i.p. injection of pregnenolone in reducing alcohol intake was not quite significant compared with the vehicle, pregnenolone at 75 mg/kg significantly (P<0.025) reduced alcohol intake. Regarding alcohol preference, acute administration of pregnenolone both at 50 mg/kg (P<0.05) and at 75 mg/kg (P<0.025) significantly reduced alcohol preference. In chronic experiments pregnenolone given for 10 consecutive days did not show a significant effect on alcohol intake and alcohol preference. Overall, although pregnenolone given i.p. acutely and significantly reduced alcohol intake and preference, the fact that chronic treatment did not show an effect diminishes its promise to be considered for the treatment of alcoholism. However, its profile of effects might be different in human alcoholics.