焦虑选择性减轻的分子和神经元基础。

Molecular and neuronal substrate for the selective attenuation of anxiety.

作者信息

Löw K, Crestani F, Keist R, Benke D, Brünig I, Benson J A, Fritschy J M, Rülicke T, Bluethmann H, Möhler H, Rudolph U

机构信息

Institute of Pharmacology and Toxicology, University of Zürich, and Swiss Federal Institute of Technology Zürich (ETH), Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.

出版信息

Science. 2000 Oct 6;290(5489):131-4. doi: 10.1126/science.290.5489.131.

DOI:10.1126/science.290.5489.131

PMID:11021797

Abstract

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 alpha2 or alpha3 GABAA (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 alpha2(H101R) point mutation but present in mice with the alpha3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by alpha2 GABAA receptors, which are largely expressed in the limbic system, but not by alpha3 GABAA receptors, which predominate in the reticular activating system.

摘要

苯二氮䓬类镇静剂用于治疗焦虑症。为了确定介导苯二氮䓬类药物抗焦虑作用的分子和神经元靶点，我们构建并分析了两个小鼠品系，其中α2或α3 GABAA（γ-氨基丁酸A型）受体分别通过敲入点突变对安定不敏感。具有α2（H101R）点突变的小鼠中安定的抗焦虑作用缺失，但具有α3（H126R）点突变的小鼠中存在该作用。这些发现表明，苯二氮䓬类药物的抗焦虑作用是由主要在边缘系统表达的α2 GABAA受体介导的，而不是由在网状激活系统中占主导地位的α3 GABAA受体介导的。