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 b een 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 produ ced significant increases in body weight and elicited marked hyperphagia as compared to a vehicle-treated control group at all time intervals as obser ved on days 1, 7, 14, 21 and 28. On the other hand, subchronic treatment wi th dehydroepiandrosterone sulfate (DHEAS) for 28 days at 10 mg/kg s.c. prod uced 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 i ntake are responsible for the reduction of body weight caused by DHEAS in t his strain of female mice. Subchronic treatment with DHEAS (10 mg/kg s.c.) also significantly (p < 0.05) suppressed progesterone-induced weight gain a nd hyperphagia as compared to the progesterone-treated group but not as com pared to the vehicle-treated control group (except on day 1). In conclusion , the results of the present study suggest that progesterone-induced hyperp hagia and weight gain can serve as a useful animal model of drug-induced ob esity. The drugs useful in this model may have implications for the treatme nt of obesity caused by disturbances of ovarian hormone secretion in female s. Furthermore, the study underscores the case of these neurosteroids for t he treatment of eating disorders. (C) 2001 Prous Science. All rights reserv ed.