{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:29:56Z","timestamp":1792798196589,"version":"4.5.0"},"reference-count":17,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5489","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2000,10,6]]},"abstract":"<jats:p>\n                    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 \u03b12 or \u03b13 GABA\n                    <jats:sub>A<\/jats:sub>\n                    (\u03b3-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 \u03b12(H101R) point mutation but present in mice with the \u03b13(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by \u03b12 GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors, which are largely expressed in the limbic system, but not by \u03b13 GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors, which predominate in the reticular activating system.\n                  <\/jats:p>","DOI":"10.1126\/science.290.5489.131","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:53:24Z","timestamp":1027749204000},"page":"131-134","source":"Crossref","is-referenced-by-count":787,"title":["Molecular and Neuronal Substrate for the Selective Attenuation of Anxiety"],"prefix":"10.1126","volume":"290","author":[{"given":"Karin","family":"Lo\u0308w","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Crestani","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Keist","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Benke","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Bru\u0308nig","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A.","family":"Benson","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Fritschy","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ru\u0308licke","sequence":"additional","affiliation":[{"name":"Biological Central Laboratory, University Hospital, Sternwartstrasse 6, CH-8091 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Bluethmann","sequence":"additional","affiliation":[{"name":"Department Pharma Research Gene Technology, F. Hoffmann\u2013La Roche Ltd., CH-4002 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns","family":"Mo\u0308hler","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zu\u0308rich, and Swiss Federal Institute of Technology Zu\u0308rich (ETH), Winterthurerstrasse 190, CH-8057 Zu\u0308rich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305133281907"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45961-3"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00803-5"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/44579"},{"key":"e_1_3_1_6_2","unstructured":"The \u03b11(H101R) point mutation in mice described in (4) was also developed by R. M. McKernan et al. [ Nature Neurosci. 3 587 (2000)]."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903590111"},{"key":"e_1_3_1_8_2","unstructured":"Details of the generation of the \u03b12(H101R) and \u03b13(H126R) mouse lines are available at Science Online (www.sciencemag.org\/feature\/data\/1052988.shl). The mice that were used in this report were backcrossed for five or six generations to the 129\/SvJ background."},{"key":"e_1_3_1_9_2","unstructured":"Cultured hippocampal pyramidal cells were chosen as a model system to confirm that the pharmacological properties of recombinant mutant \u03b12 GABA A receptors can also be demonstrated for GABA A receptors in mutant mice."},{"key":"e_1_3_1_10_2","unstructured":"Experimental details are available at Science Online (www.sciencemag.org\/feature\/data\/1052988.shl)."},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(88)90259-6"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-6357(89)80010-5"},{"key":"e_1_3_1_13_2","first-page":"180","volume":"92","author":"Lister R. G.","year":"1987","unstructured":"Lister R. G., Psychopharmacology 92, 180 (1987).","journal-title":"Psychopharmacology"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.3109\/10799899309073673"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11939"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980112)390:2<194::AID-CNE3>3.0.CO;2-X"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5860"},{"key":"e_1_3_1_18_2","unstructured":"We thank Y. Lang for blastocyst injection; P. Fakitsas and C. Michel for performing immunoblot autoradiography and ligand binding experiments; C. Sidler for hippocampal cell culture; D. Blaser H. Pochetti and G. Schmid for animal care; H. Westphal for EIIa-cre mice; H. Hengartner for E14 embryonic stem cells; and E. M. Simpson for mEMS32 embryonic stem cells. Supported by a grant from the Swiss National Science Foundation."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.290.5489.131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T05:20:13Z","timestamp":1705123213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.290.5489.131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10,6]]},"references-count":17,"journal-issue":{"issue":"5489","published-print":{"date-parts":[[2000,10,6]]}},"alternative-id":["10.1126\/science.290.5489.131"],"URL":"https:\/\/doi.org\/10.1126\/science.290.5489.131","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1005653.67158","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,10,6]]}}}