Blockade of Brain γ-Aminobutyric Acid a Receptors Antagonizes Hypnotic Action of Isoflurane in Rats―GABA Receptor and Isoflurane Induced Hypnosis英文文献资料.docVIP

Journal of Behavioral and Brain Science, 2011, 1, 188-193 doi:10.4236/jbbs.2011.13025 Published Online August 2011 (http://www.SciRP.org/journal/jbbs) Blockade of Brain γ-Aminobutyric Acid A Receptors Antagonizes Hypnotic Action of Isoflurane in Rats* ―GABAA Receptor and Isoflurane Induced Hypnosis Ming Xiong , Ralph L. da Graca , Jing Li, Harshitha Kota, Jiang-Hong Ye # # ? Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, USA E-mail: Xiong@, rdagracamd@, Jingli_umdnj@, kotahr@, Received May 23, 2011; revised July 19, 2011; accepted July 28, 2011 ? ye@ Abstract Although in vitro studies have demonstrated that isoflurane potentiates the function of γ-aminobutyric acid A receptors (GABAARs), the in vivo data are controversial. To determine if GABAARs contribute to the loss-of righting reflex (LORR) induced by isoflurane, we studied the LORR in the absence and presence of gabazine, a competitive GABAAR antagonist, in Sprague-Dawley rats anesthetized with either isoflurane or ketamine. Administration of isoflurane and ketamine induced LORR in a dose-dependent manner. Gabazine significantly antagonized the effect of isoflurane and shifted the dose response curve to the right. In addition, gabazine prolonged the onset time of LORR induced by isoflurane. Ketamine induced LORR was not af- fected by gabazine. This indicates that centrally administered gabazine selectively blocks the effect of isoflurane, and the effect of gabazine is not due to a non-specific CNS excitatory action. These results sug- gest that the hypnotic effect of isoflurane is at least in part mediated by GABAARs. Keywords: GABAA Receptors, Gabazine, General Anesthetics, Ketamine, Loss-of Righting Reflex 1. Introduction previous animal stu