THE EFFECT OF CHRONIC BENZODIAZEPINES EXPOSURE ON BODY WEIGHT IN RATS

• Published in: Pharmacological research 1998-03, Vol.37 (3), p.179-189
• Main Authors: JING, XIN, WALA, ELZBIETA P., SLOAN, JEWELL W.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - antagonists & inhibitors; Anti-Anxiety Agents - pharmacology; Body Weight - drug effects; body weight, benzodiazepines, flumazenil, chronic exposure; Diazepam - administration & dosage; Diazepam - antagonists & inhibitors; Diazepam - pharmacology; Dose-Response Relationship, Drug; Female; Flumazenil - administration & dosage; Flumazenil - pharmacology; Flunitrazepam - administration & dosage; Flunitrazepam - antagonists & inhibitors; Flunitrazepam - pharmacology; GABA Modulators - administration & dosage; GABA Modulators - pharmacology; Male; Nordazepam - administration & dosage; Nordazepam - antagonists & inhibitors; Nordazepam - pharmacology; Oxazepam - administration & dosage; Oxazepam - antagonists & inhibitors; Oxazepam - pharmacology; Rats; Rats, Sprague-Dawley; Sex Factors; Time Factors; Weight Gain - drug effects
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1997.0289

Changes in body weight (BW) in female rats treated for 5 weeks (wk) with weekly subcutaneous implantation of silastic capsules containing different benzodiazepines (BZs): diazepam (DZ) 90, 180, 360 and 540 mg wk−1; nordiazepam (ND) 600 mg wk−1; oxazepam (OX) 600 mg wk−1and flunitrazepam (FN) 540 mg wk−1and in male rats exposed to DZ (540 mg wk−1) were evaluated herein. Rats (female and male) implanted with empty capsules served as controls. The BW gain was significantly higher in male than in female rats (both DZ-treated and controls). The BW gain increased with increasing doses of DZ but slowed with time of exposure. In comparison to control rats, the BW gain was significantly higher in DZ- (540 mg wk−1) and OX- but not in ND- and FN-treated female rats. However, the differences between BZs were not of statistical significance. In rats exposed to empty capsules (male, female); DZ (male); ND and OX (female) the BW gain increased with time (1–4 wk) while in rats exposed to DZ and FN (female) the BW stabilised within 2 wk. Acute injection of the central BZ receptor antagonist, flumazenil (40 mg kg−1, i.v., 5th wk of chronic exposure), tended to inhibit the time-related BW gain in rats exposed to empty capsules (male, female), DZ (male), ND and OX (female) but did not affect the BW in DZ- (540 mg wk−1) and FN-exposed rats (female) where BW stabilised prior to FLU injection. Repeated administration of flumazenil (30 mg kg−1wk−1, i.p.) did not affect the BW gain in DZ- and ND-treated female rats. The present data indicate that different BZs have different effects on BW gain in the rat suggesting that different subtypes of BZ receptors are involved.