Blockade of Brain γ-Aminobutyric Acid a Receptors Antagonizes Hypnotic Action of Isoflurane in Rats―GABA Receptor and Isoflurane Induced Hypnosis

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 affected 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 suggest that the hypnotic effect of isoflurane is at least in part mediated by GABAARs.