Barnhill J G, Ciraulo D A, Greenblatt D J, Faggart M A, Harmatz J S
Department of Psychiatry, Tufts-New England Medical Center, Boston, Massachusetts.
J Pharmacol Exp Ther. 1991 Sep;258(3):812-9.
Benzodiazepine receptor binding and open-field response were examined in male CD-1 mice after 6 weeks on a liquid diet providing either 36% ethanol or maltose-dextrin derived calories. In vivo binding of [3H]Ro15-1788, open-field activity and cortex and plasma concentrations were measured over a range of clonazepam doses (0.05-2.0 mg/kg). Mean +/- S.D. of ethanol consumption was 19.3 +/- 1.1 g/kg/day. Clonazepam concentration in plasma and cortex was related linearly to dose in both groups. Cortex concentrations exceeded plasma concentrations at all doses. Ethanol-consuming mice showed considerably less decrease in measures of horizontal and stereotypic activity at each dose studied. Mean in vivo IC50 was 20.9 +/- 4.0 ng/g for the control mice and 40.2 +/- 7.6 ng/g (P less than .001) in the ethanol-consuming mice. In vitro binding studies found a marked decrease in maximum binding in cortex (37%) with an increase in Kd (66%). Chronic ethanol can influence the acute effects of single doses of clonazepam and both in vivo and in vitro measures of benzodiazepine receptor binding.
在以提供36%乙醇或麦芽糖糊精热量的液体饮食喂养6周后的雄性CD-1小鼠中，检测了苯二氮䓬受体结合和旷场反应。在一系列氯硝西泮剂量（0.05 - 2.0 mg/kg）下，测量了[3H]Ro15 - 1788的体内结合、旷场活动以及皮质和血浆浓度。乙醇摄入量的均值±标准差为19.3±1.1 g/kg/天。两组中血浆和皮质中的氯硝西泮浓度均与剂量呈线性关系。在所有剂量下，皮质浓度均超过血浆浓度。在每个研究剂量下，摄入乙醇的小鼠在水平和刻板活动测量中的降低幅度明显较小。对照小鼠的体内半数抑制浓度（IC50）均值为20.9±4.0 ng/g，摄入乙醇的小鼠为40.2±7.6 ng/g（P <.001）。体外结合研究发现，皮质中的最大结合显著降低（37%），解离常数（Kd）增加（66%）。慢性乙醇可影响单剂量氯硝西泮的急性效应以及苯二氮䓬受体结合的体内和体外测量结果。
