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gabaa receptor α subunits differentially contribute to diazepam tolerance after chronic treatmentgabaa受体α亚基不同导致慢性治疗后安定宽容
GABAA Receptor a Subunits Differentially Contribute to Diazepam Tolerance after Chronic Treatment 1,2 1 3 4 3,5 Christiaan H. Vinkers *, Ruud van Oorschot , Elsebet Ø. Nielsen , James M. Cook , Henrik H. Hansen , Lucianne Groenink1, Berend Olivier 1,6, Naheed R. Mirza3,7 1 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands, 2 Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands, 3 NeuroSearch A/S, NsDiscovery, Ballerup, Denmark, 4 Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America, 5 Gubra ApS, Hørsholm, Denmark, 6 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America, 7 Aniona ApS, Ballerup, Denmark Abstract Background: Within the GABA -receptor field, two important questions are what molecular mechanisms underlie A benzodiazepine tolerance, and whether tolerance can be ascribed to certain GABAA-receptor subtypes. Methods: We investigated tolerance to acute anxiolytic, hypothermic and sedative effects of diazepam in mice exposed for 28-days to non-selective/selective GABAA-receptor positive allosteric modulators: diazepam (non-selective), bretazenil (partial non-selective), zolpidem (a 3 1 selective) and TPA023 (a2/3 selective). In-vivo
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