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Löw, Karin; Crestani, Florence; Keist, Ruth; Benke, Dietmar; Brünig, Ina; Benson, Jack A.; Fritschy, Jean-Marc; Rülicke, Thomas; Bluethmann, Horst; Möhler, Hanns; Rudolph, Uwe
Science (American Association for the Advancement of Science), 10/2000, Letnik: 290, Številka: 5489Journal Article
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 α2 or α3 GABAA(γ-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 α2(H101R) point mutation but present in mice with the α3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by α2 GABAAreceptors, which are largely expressed in the limbic system, but not by α3 GABAAreceptors, which predominate in the reticular activating system.
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