EVIDENCE SUGGESTING THAT GONADAL-HORMONES INFLUENCE BENZODIAZEPINE WITHDRAWAL-INDUCED WEIGHT-LOSS IN RATS

1. In experimental animals, benzodiazepine (BZ) withdrawal syndrome in cludes anorexia and acute weight loss. The literature shows several se x-based differences in the expression of BZ dependence; however, the a uthors did not find studies dealing with the influence of gonadal horm ones on BZ withdrawal-induced weight loss. Thus, this study was design ed to investigate the effects of castration on diazepam (DZ) withdrawa l-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 sur gery, the animals were injected i.p. with DZ (4 mg kg(-1)day(-1)) or a ppropriate 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 per centage of those recorded in the morning of day 28. 3. Sham-operated f emale rats from the group DZ-VEH showed a small but statistically sign ificant weight loss on days 29 and 30 (P < 0.05) when compared with gr oups VEH-VEH and DZ-DZ. Ovariectomized rats, however, did not show any significant change in body weight from days 29-34. 4. Sham-operated m ale rats did not exhibit any significant weight loss after DZ withdraw al. Orchidectomized animals, however, showed a small but statistically significant weight loss on day 31 (P < 0.05) when compared with group s VEH-VEH and DZ-DZ. 5. These results show a gonadal influence on DZ w ithdrawal-induced weight loss in Wistar rats; in particular, they also suggest that female hormones (progesterone and/or estrogen) facilitat e whilst male hormones inhibit this phenomenon.