オバタ　ヒデアキ   OBATA Hideaki   小幡　英章    所属   埼玉医科大学  医学部 総合医療センター　麻酔科（麻酔科、産科麻酔科）    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	The influence of manipulations to alter ambient GABA concentrations on the hypnotic and immobilizing actions produced by sevoflurane, propofol, and midazolam
掲載誌名	正式名：NEUROPHARMACOLOGY ISSNコード：00283908
出版社	PERGAMON-ELSEVIER SCIENCE LTD
巻・号・頁	61(1-2),172-180頁
著者・共著者	Koichi Nishikawa,Kazuhiro Kubo,Hideaki Obata,Yuchio Yanagawa,Shigeru Saito
発行年月	2011/07
概要	Recent studies have suggested that extrasynaptic GABA(A) receptors, which contribute tonic conductance, are important targets for general anesthetics. We tested the hypothesis that manipulations designed to alter ambient GABA concentrations (tonic conductance) would affect hypnotic (as indicated by loss of righting reflex, LORR) and immobilizing (as indicated by loss of tail-pinch withdrawal reflex, LTWR) actions of sevoflurane, propofol, and midazolam. Two manipulations studied were 1) the genetic absence of glutamate decarboxylase (GAD) 65 gene (GAD65-/-), which purportedly reduced ambient GABA concentrations, and 2) the pharmacological manipulation of GABA uptake using GABA transporter inhibitor (NO-711). The influence of these manipulations on cellular and behavioral responses to the anesthetics was studied using behavioral and electrophysiological assays. HPLC revealed that GABA levels in GAD65-/- mice were reduced in the brain (76.7% of WT) and spinal cord (68.5% of WT). GAD65-/- mice showed a significant reduction in the duration of LORR and LTWR produced by propofol and midazolam, but not sevoflurane. NO-711 (3 mg/kg, ip) enhanced the duration of LORR and LTWR by propofol a
DOI	10.1016/j.neuropharm.2011.03.025
PMID	21497611