Molecular and neuronal substrate for the selective attenuation of anxiety
Molecular and neuronal substrate for the selective attenuation of anxiety
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DOI：
10.1126/science.290.5489.131
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发表时间：
2000-10-06
期刊：
影响因子：
56.9
通讯作者：
Rudolph, U
中科院分区：
文献类型：
--
作者：
Löw, K;Crestani, F;Rudolph, U
苯二氮卓类镇静剂用于治疗焦虑症。为了确定介导苯二氮卓类药物抗焦虑作用的分子和神经元靶标，我们生成并分析了两个小鼠品系，其中α2或α3GABA(A)（A型γ-氨基丁酸）受体分别通过敲入点突变而对地西泮不敏感。地西泮的抗焦虑作用在具有 α2(H101R) 点突变的小鼠中不存在，但在具有 α3(H126R) 点突变的小鼠中存在。这些发现表明，苯二氮卓类药物的抗焦虑作用是由 α2 GABA(A) 受体介导的，α2 GABA(A) 受体主要在边缘系统中表达，但不是由 α3 GABA(A) 受体介导，α3 GABA(A) 受体在网状激活系统中占主导地位。
Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the alpha 2 or alpha 3 GABA(A) (gamma-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the alpha 2(H101R) point mutation but present in mice with the alpha 3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by alpha 2 GABA(A) receptors, which are largely expressed in the limbic system, but not by alpha 3 GABA(A) receptors, which predominate in the reticular activating system.