{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:53:29Z","timestamp":1790898809070,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,11,22]]},"abstract":"<jats:p>\n                    Overactivity of the dopaminergic system in the brain is considered to be a contributing factor to the development and symptomatology of schizophrenia. Therefore, the GABAergic control of dopamine functions was assessed by disrupting the gene encoding the \u03b13 subunit of the GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor. \u03b13 knockout (\u03b13KO) mice exhibited neither an obvious developmental defect nor apparent morphological brain abnormalities, and there was no evidence for compensatory up-regulation of other major GABA\n                    <jats:sub>A<\/jats:sub>\n                    -receptor subunits. Anxiety-related behavior in the elevated-plus-maze test was undisturbed, and the anxiolytic-like effect of diazepam, which is mediated by \u03b12-containing GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors, was preserved. As a result of the loss of \u03b13 GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors, the GABA-induced whole-cell current recorded from midbrain dopamine neurons was significantly reduced. Spontaneous locomotor activity was slightly elevated in \u03b13KO mice. Most notably, prepulse inhibition of the acoustic startle reflex was markedly attenuated in the \u03b13KO mice, pointing to a deficit in sensorimotor information processing. This deficit was completely normalized by treatment with the antipsychotic D2-receptor antagonist haloperidol. The amphetamine-induced hyperlocomotion was not altered in \u03b13KO mice compared with WT mice. These results suggest that the absence of \u03b13-subunit-containing GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors induces a hyperdopaminergic phenotype, including a severe deficit in sensorimotor gating, a common feature among psychiatric conditions, including schizophrenia. Hence, agonists acting at \u03b13-containing GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors may constitute an avenue for an effective treatment of sensorimotor-gating deficits in various psychiatric conditions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0508752102","type":"journal-article","created":{"date-parts":[[2005,11,11]],"date-time":"2005-11-11T20:25:08Z","timestamp":1131740708000},"page":"17154-17159","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":169,"title":["A schizophrenia-related sensorimotor deficit links \u03b13-containing GABA\n                    <sub>A<\/sub>\n                    receptors to a dopamine hyperfunction"],"prefix":"10.1073","volume":"102","author":[{"given":"B. K.","family":"Yee","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland; Laboratory of Behavioral Neurobiology and Department of Chemistry and Applied Biosciences and Collegium Helveticum, Swiss Federal Institute of Technology Z\u00fcrich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS P104, Stanford, CA 94305-5485; and Roche Center..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Keist","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland; Laboratory of Behavioral Neurobiology and Department of Chemistry and Applied Biosciences and Collegium Helveticum, Swiss Federal Institute of Technology Z\u00fcrich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS P104, Stanford, CA 94305-5485; and Roche Center..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"von Boehmer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland; Laboratory of Behavioral Neurobiology and Department of Chemistry and Applied Biosciences and Collegium Helveticum, Swiss Federal Institute of Technology Z\u00fcrich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS P104, Stanford, CA 94305-5485; and Roche Center..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Studer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland; Laboratory of Behavioral Neurobiology and Department of Chemistry and Applied Biosciences and Collegium Helveticum, Swiss Federal Institute of Technology Z\u00fcrich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS P104, Stanford, CA 94305-5485; and Roche Center..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Benke","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland; Laboratory of Behavioral Neurobiology and Department of Chemistry and Applied Biosciences and Collegium Helveticum, Swiss Federal Institute of Technology Z\u00fcrich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS P104, Stanford, CA 94305-5485; and Roche Center..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Hagenbuch","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland; Laboratory of Behavioral Neurobiology and Department of Chemistry and Applied Biosciences and Collegium Helveticum, Swiss Federal Institute of Technology Z\u00fcrich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS P104, Stanford, CA 94305-5485; and Roche Center..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland; Laboratory of Behavioral Neurobiology and Department of Chemistry and Applied Biosciences and Collegium Helveticum, Swiss Federal Institute of Technology Z\u00fcrich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, MSLS P104, Stanford, CA 94305-5485; and Roche Center..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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