A Pharmacogenetic 'Restriction-of-Function' Approach Reveals Evidence for Anxiolytic-Like Actions Mediated by α5-Containing GABAA Receptors in Mice.

ABSTRACT: Benzodiazepines have been widely used for their anxiolytic actions. However, the contribution of GABAA receptor subtypes to anxiolysis is still controversial. Studies with mutant mice harboring diazepam-insensitive α-subunits α1, α2, α3, or α5 have revealed that α2-containing GABAA receptors (α2-GABAARs) are required for diazepam-induced anxiolysis, with no evidence for an involvement of any other α-subunit, whereas TP003, described as a selective modulator of α3-containing GABAA receptors, was shown to be anxiolytic. Here, we describe a novel, systematic approach to evaluate the role of positive allosteric modulation of each of the four diazepam-sensitive α-subtypes in anxiety-related behavioral paradigms. By combining H to R point mutations in three out of the four diazepam-sensitive α-s

SUBMITTER: Behlke LM 

PROVIDER: S-EPMC4987847 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature