Jing X, Wala E P, Sloan J W
Department of Anesthesiology, University of Kentucky, College of Medicine, Lexington 40536-0216, USA.
Pharmacol Res. 1998 Mar;37(3):179-89. 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-1 and flunitrazepam (FN) 540 mg wk-1 and 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-1 wk-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.
本研究评估了雌性大鼠皮下每周植入含不同苯二氮䓬类药物（BZs）的硅橡胶胶囊5周后体重（BW）的变化，这些药物包括：地西泮（DZ）90、180、360和540mg/周；去甲西泮（ND）600mg/周；奥沙西泮（OX）600mg/周和氟硝西泮（FN）540mg/周，同时也评估了雄性大鼠暴露于DZ（540mg/周）后的体重变化。植入空胶囊的大鼠（雌雄皆有）作为对照。雄性大鼠的体重增加显著高于雌性大鼠（包括接受DZ治疗的和对照的）。体重增加随DZ剂量增加而升高，但随暴露时间延长而减缓。与对照大鼠相比，接受DZ（540mg/周）和OX治疗的雌性大鼠体重增加显著高于接受ND和FN治疗的雌性大鼠。然而，不同BZs之间的差异无统计学意义。在植入空胶囊的大鼠（雄性、雌性）、接受DZ治疗的雄性大鼠、接受ND和OX治疗的雌性大鼠中，体重增加随时间（1 - 4周）而升高，而在接受DZ和FN治疗的雌性大鼠中，体重在2周内趋于稳定。急性注射中枢BZ受体拮抗剂氟马西尼（40mg/kg，静脉注射，慢性暴露第5周），倾向于抑制植入空胶囊的大鼠（雄性、雌性）、接受DZ治疗的雄性大鼠、接受ND和OX治疗的雌性大鼠中与时间相关的体重增加，但不影响接受DZ（540mg/周）和FN治疗的雌性大鼠的体重，在注射氟马西尼之前其体重已趋于稳定。重复注射氟马西尼（30mg/kg/周，腹腔注射）不影响接受DZ和ND治疗的雌性大鼠的体重增加。目前的数据表明，不同的BZs对大鼠体重增加有不同影响，提示涉及不同亚型的BZ受体。
