Gene Knockout of the α6 Subunit of the γ-Aminobutyric Acid Type A Receptor: Lack of Effect on Responses to Ethanol, Pentobarbital, and General Anesthetics

摘要: The alpha6 subunit of the gamma-aminobutyric acid type A receptor (GABA(A)-R) has been implicated in mediating intoxicating effects ethanol and motor ataxic general anesthetics. To test this hypothesis, we used gene targeting embryonic stem cells to create mice lacking a functional gene. Homozygous are viable fertile have grossly normal cerebellar cytoarchitecture. Northern blot reverse transcriptase-polymerase chain reaction analyses demonstrated that event disrupted production mRNA. Autoradiography histological sections adult brains diazepam-insensitive binding [3H]Ro15-4513 granule cell layer wild-type was completely absent homozygous mice. Cerebellar GABA(A)-R density unchanged mutant mice; however, apparent affinity for muscimol markedly reduced. Sleep time response injection after pretreatment with vehicle or Ro15-4513 did not differ between genotypes. pentobarbital loss righting reflex tail clamp stimulus anesthetized volatile anesthetics also Thus, is required development, viability, fertility does seem be critical unique component neuronal pathway hypnotic effect its antagonism by Similarly, involved behavioral responses pentobarbital.