Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK.
J Psychopharmacol. 1992 Jan;6(3):364-9. doi: 10.1177/026988119200600304.
The regulation of the subunit composition of GABA(A) receptors may be a mechanism by which tolerance to the effects of benzodiazepines occurs. We have investigated this hypothesis by examining the levels of mRNA which codes for the GABA(A) β1, 2, 3 and γ2 subunits. Male Wistar rats were injected once daily with either flurazepam or vehicle, sacrificed after treatment regimes of up to 32 days and the brain RNA isolated. The levels of specific mRNAs encoding the receptor subunits were measured relative to a β-actin standard. No changes were found in the levels of these mRNAs at any time points. Our results lend no support to the hypothesis that alterations in the β or γ2 subunit composition of GABA(A) receptors is the mechanism responsible for the development of tolerance to, or dependence on, benzodiazepines.
GABA(A) 受体亚基组成的调节可能是苯二氮䓬类药物作用产生耐受性的机制。我们通过检测编码 GABA(A)β1、β2、β3 和 γ2 亚基的 mRNA 水平来研究这一假说。雄性 Wistar 大鼠每天接受氟西泮或载体注射，治疗 32 天后处死并分离脑 RNA。用 β-肌动蛋白标准品相对测量受体亚基的特定 mRNA 水平。在任何时间点都未发现这些 mRNA 水平的变化。我们的结果不支持这样的假说，即 GABA(A) 受体β或γ2 亚基组成的改变是导致对苯二氮䓬类药物产生耐受性或依赖性的机制。
