Evidence suggesting that gonadal hormones influence benzodiazepine withdrawal-induced weight loss in rats

1. In experimental animals, benzodiazepine (BZ) withdrawal syndrome includes anorexia and acute weight loss. The literature shows several sex-based differences in the expression of BZ dependence; however, the authors did not find studies dealing with the influence of gonadal hormones on BZ withdrawal-induced weight loss. Thus, this study was designed to investigate the effects of castration on diazepam (DZ) withdrawal-induced weight loss in rats. 2. Male (260-330 g) or female (220-260 g) Wistar rats were anesthetized with ether and submitted to surgical castration or sham-operation. Seven days later, recovered from the surgery, the animals were injected i.p. with DZ (4 mg kg-1 day-1) or appropriate vehicle (VEH; 2 ml kg-1 kg-1 day-1) for 28 days. In the next 7 days, the rats received the same doses of DZ (four groups) or VEH (eight groups). Weights of all animals were recorded daily to the nearest gram at 09:00 h. To assess the degree of weight loss and make statistical comparisons, weights over days 29-34 were expressed as percentage of those recorded in the morning of day 28. 3. Sham-operated female rats from the group DZ-VEH showed a small but statistically significant weight loss on days 29 and 30 (P < 0.05) when compared with groups VEH-VEH and DZ-DZ. Ovariectomized rats, however, did not show any significant change in body weight from days 29-34. 4. Sham-operated male rats did not exhibit any significant weight loss after DZ withdrawal. Orchidectomized animals, however, showed a small but statistically significant weight loss on day 31 (P < 0.05) when compared with groups VEH-VEH and DZ-DZ. 5. These results show a gonadal influence on DZ withdrawal-induced weight loss in Wistar rats; in particular, they also suggest that female hormones (progesterone and/or estrogen) facilitate whilst male hormones inhibit this phenomenon.