PT  - JOURNAL ARTICLE
AU  - Löw, Karin
AU  - Crestani, Florence
AU  - Keist, Ruth
AU  - Benke, Dietmar
AU  - Brünig, Ina
AU  - Benson, Jack A.
AU  - Fritschy, Jean-Marc
AU  - Rülicke, Thomas
AU  - Bluethmann, Horst
AU  - Möhler, Hanns
AU  - Rudolph, Uwe
TI  - Molecular and Neuronal Substrate for the Selective Attenuation of Anxiety
AID  - 10.1126/science.290.5489.131
DP  - 2000 Oct 06
TA  - Science
PG  - 131--134
VI  - 290
IP  - 5489
4099  - http://science.sciencemag.org/content/290/5489/131.short
4100  - http://science.sciencemag.org/content/290/5489/131.full
SO  - Science2000 Oct 06; 290
AB  - 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 GABAA receptors, which are largely expressed in the limbic system, but not by α3 GABAAreceptors, which predominate in the reticular activating system.