Expression of alpha 1, alpha 5, and gamma 2 GABAA receptor subunit mRNAs measured in situ in rat hippocampus and cortex following chronic flurazepam administration.
Expression of alpha 1, alpha 5, and gamma 2 GABAA receptor subunit mRNAs measured in situ in rat hippocampus and cortex following chronic flurazepam administration.
复制标题
长期服用氟西泮后，在大鼠海马和皮质中原位测量 α 1、α 5 和 γ 2 GABAA 受体亚基 mRNA 的表达。
DOI：
10.1007/bf02821559
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Chiu,TH
中科院分区：
文献类型：
--
作者：
Tietz,EI;Huang,X;Weng,X;Rosenberg,HC;Chiu,TH
大鼠长期服用苯二氮卓类药物可导致体内抗惊厥耐受。对给药1wk的体外海马片的研究表明，CA1区GABA介导的抑制作用减少，GABA激动剂和苯二氮卓类药物抑制CA1锥体细胞诱发反应的效力降低。为探讨苯二氮类药物耐受的分子基础，采用原位杂交技术检测了慢性氟西安定治疗大鼠海马结构和额叶皮质中α-1、α-5和γ-2受体亚单位的表达。停药2d后，α1在CA1区(35%~40%)和皮质II~III、IV层(50%~60%)的表达呈局限性下降，而α5和γ2mRNA的表达无明显变化。皮质α1亚单位基因表达的下降与其他慢性苯二氮类药物治疗方案的报道相似。这是首次报道α1亚单位基因在海马区的表达减少。
Prolonged benzodiazepine treatment of rats results in anticonvulsant tolerance in vivo. Studies of in vitro hippocampal slices following 1 wk flurazepam administration show reduced GABA-mediated inhibition in the CA1 region, and a decrease in GABAAagonist and benzodiazepine potency to inhibit CA1 pyramidal cell-evoked responses. To investigate the molecular basis of benzodiazepine tolerance in the hippocampus,in situhybridization techniques were used to evaluate the expression of the mRNAs for the α1, α5, and γ2subunits of the GABAAreceptor in the hippocampal formation and frontal cortex of chronic flurazepam-treated rats. A discretely localized decrease in α1, but not α5or γ2mRNA expression was found in the CA1 region (35–40%) and in layers II–III and IV of cortex (50–60%) 2 d after cessation of flurazepam treatment. The decrease in the expression of α1subunit mRNA in cortex is similar to that reported following other chronic benzodiazepine treatment regimens. This is the first report of a reduction in α1subunit mRNA expression in the hippocampal formation.