Mutation of the inhibitory ethanol site in GABA_A ρ1 receptors promotes tolerance to ethanol-induced motor incoordination.

ABSTRACT: Genes encoding the ρ1/2 subunits of GABA_A receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine). We generated ρ1 (T6'Y) knockin (KI) mice using CRISPR/Cas9 to test the behavioral importance of the inhibitory actions of ethanol on this receptor. Both ρ1

SUBMITTER: Blednov YA 

PROVIDER: S-EPMC5543808 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature