Subchronic studies on modulation of feeding behavior and body weight by neurosteroids in female mice.

Neurosteroids have shown promising therapeutic potential in a wide variety of neuropsychiatric and cognitive disorders. However, little research has been done on their role for the treatment of eating disorders and regulation of energy balance in the body. In the present study, subchronic treatment with the neuroactive steroid progesterone (10 mg/kg s.c.) for 28 days produced significant increases in body weight and elicited marked hyperphagia as compared to a vehicle-treated control group at all time intervals as observed on days 1, 7, 14, 21 and 28. On the other hand, subchronic treatment with dehydroepiandrosterone sulfate (DHEAS) for 28 days at 10 mg/kg s.c. produced significant (p < 0.05) decreases in body weight and food intake at all time intervals on days 1, 7, 14 and 28 suggesting that decreases in food intake are responsible for the reduction of body weight caused by DHEAS in this strain of female mice. Subchronic treatment with DHEAS (10 mg/kg s.c.) also significantly (p < 0.05) suppressed progesterone-induced weight gain and hyperphagia as compared to the progesterone-treated group but not as compared to the vehicle-treated control group (except on day 1). In conclusion, the results of the present study suggest that progesterone-induced hyperphagia and weight gain can serve as a useful animal model of drug-induced obesity. The drugs useful in this model may have implications for the treatment of obesity caused by disturbances of ovarian hormone secretion in females. Furthermore, the study underscores the use of these neurosteroids for the treatment of eating disorders.