Crestani Florence, Rudolph Uwe
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, Massachusetts, USA; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
Adv Pharmacol. 2015;72:37-51. doi: 10.1016/bs.apha.2014.10.001. Epub 2014 Dec 4.
GABAA receptors are the major inhibitory neurotransmitter receptors in the brain. They are heteropentamers that are typically classified according to their α subunits. By rendering each of the benzodiazepine-sensitive α subunits (α1, α2, α3, and α5) insensitive to modulation by classical benzodiazepines by His to Arg point mutations in knock-in mice, we were able to identify behavioral functions mediated by different GABAA receptor subtypes, which led to the development of novel therapeutic strategies. In this chapter, we provide a largely chronological overview on behavioral studies on GABAA receptor mutant mice at the Institute of Pharmacology and Toxicology at the University of Zurich.
GABAA受体是大脑中主要的抑制性神经递质受体。它们是异五聚体,通常根据其α亚基进行分类。通过在敲入小鼠中利用组氨酸到精氨酸的点突变使每个对苯二氮䓬敏感的α亚基(α1、α2、α3和α5)对经典苯二氮䓬的调节不敏感,我们能够确定不同GABAA受体亚型介导的行为功能,这促成了新治疗策略的开发。在本章中,我们按时间顺序大致概述了苏黎世大学药理学和毒理学研究所对GABAA受体突变小鼠的行为研究。