Mosaddeghi M, Burke T F, Moerschbaecher J M
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans.
J Pharmacol Exp Ther. 1992 Nov;263(2):639-45.
Mice received i.p. injections of either saline or drug before i.p. administration of [3H]Ro 15-1788 (flumazenil), a selective benzodiazepine (BZD) receptor antagonist. Subjects were decapitated and six brain regions (cortex, cerebellum, striatum, hippocampus, hypothalamus and brain stem) were analyzed for the levels of tritium present in each tissue. Benzyl, ethyl and methyl alcohol enhanced in vivo binding of [3H]Ro 15-1788 in a dose-dependent manner in all brain regions studied with mean ED50 values of 2.4, 34.8 and 38.4% volume/kg body weight, respectively. Lorazepam (18 mg/kg) completely blocked effects of benzyl, ethyl and methyl alcohol to increase [3H]Ro 15-1788 binding. These data indicate that the alcohol-induced increases in [3H]Ro 15-1788 binding occurred at the level of the BZD receptor. In addition, these alcohols did not alter the in vivo binding of [3H]diprenorphine, an opioid receptor ligand, further indicating the selective effect of alcohol on BZD receptors. Administration of lorazepam or alprazolam produced a dose-dependent decrease in the binding of [3H]Ro 15-1788 to brain tissue after administration of either saline or 30% volume/kg ethanol. However, low doses of alprazolam increased binding of [3H]Ro 15-1788 in the absence of ethanol. Together, these results suggest that ethanol produces an increase in the number of BZD binding sites in vivo. These alcohol-induced alterations in BZD receptor binding may mediate, in part, the anxiolytic or sedative properties of ethanol.
在腹腔注射选择性苯二氮䓬（BZD）受体拮抗剂[3H]Ro 15-1788（氟马西尼）之前，给小鼠腹腔注射生理盐水或药物。将实验对象断头，分析六个脑区（皮层、小脑、纹状体、海马体、下丘脑和脑干）中各组织的氚水平。苄醇、乙醇和甲醇在所有研究的脑区中均以剂量依赖方式增强[3H]Ro 15-1788的体内结合，平均半数有效剂量（ED50）值分别为2.4、34.8和38.4%体积/千克体重。劳拉西泮（18毫克/千克）完全阻断了苄醇、乙醇和甲醇增加[3H]Ro 15-1788结合的作用。这些数据表明，酒精诱导的[3H]Ro 15-1788结合增加发生在BZD受体水平。此外，这些醇类并未改变阿片受体配体[3H]二丙诺啡的体内结合，进一步表明酒精对BZD受体的选择性作用。在注射生理盐水或30%体积/千克乙醇后，给予劳拉西泮或阿普唑仑会导致[3H]Ro 15-1788与脑组织的结合呈剂量依赖性降低。然而，低剂量的阿普唑仑在无乙醇的情况下会增加[3H]Ro 15-1788的结合。总之，这些结果表明乙醇在体内会增加BZD结合位点的数量。这些酒精诱导的BZD受体结合改变可能部分介导了乙醇的抗焦虑或镇静特性。
