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

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 22; no. 2; pp. 425 - 433
• Main Authors: Pires, JoséG.P., Monteiro, Karina C., Alvarenga, Simone O., Costa, Marcela G.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.1998; Elsevier
• Subjects: Animals; Anorexia - chemically induced; Anti-Anxiety Agents - adverse effects; Anti-Anxiety Agents - pharmacology; benzodiazepines; Biological and medical sciences; dependence; diazepam; Diazepam - adverse effects; Diazepam - pharmacology; Drug toxicity and drugs side effects treatment; Female; Gonadal Steroid Hormones - pharmacology; gonads; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Orchiectomy; Ovariectomy; Pharmacology. Drug treatments; Rats; Rats, Wistar; sex hormones; Substance Withdrawal Syndrome - physiopathology; weight loss; Weight Loss - drug effects; Wistar rats; withdrawal; vehicle for diazepam; Wistar rats; benzodiazepines; sex hormones; analysis of variance; diazepam; gonads; weight loss; dependence; withdrawal; standard error of the mean; Orchidectomy; Ovariectomy; Rat; Psychotropic; Toxicity; Rodentia; Weight loss; Male; Vertebrata; Mammalia; Tranquillizer; Surgery; Animal; Benzodiazepine derivatives; Female; Sexual dimorphism; Sex steroid hormone; Withdrawal syndrome; Diazepam
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/S0278-5846(98)00014-1

1. 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. 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 −1day −1) or appropriate vehicle (VEH; 2 ml kg −1kg −1day −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. 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. 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. 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.