Gabra6100Q allele Sprague-Dawley rats have a higher sensitivity to hypnosis induced by isoflurane and ethanol than the wild type rats

Background: The neurobiological mechanisms underlying how general anesthetics render a patient's unconsciousness (hypnosis) remains elusive. The role of the cerebellum in hypnosis induced by general anesthetics is unknown. Gabra6^100Q allele Sprague-Dawley (SD) rats have a naturally occurring single nucleotide polymorphism in the GABA_A receptor α6 subunit gene that is expressed exclusively in cerebellum granule cells. Methods: We examined the loss of righting reflex (LORR) induced by isoflurane, and ethanol in Gabra6^100Q rats compared with those in wild type (WT) SD rats. We also examined the change of c-Fos expression induced by isoflurane exposure in cerebellum granule cells of both mutant and WT rats. Results: Gabra6^100Q rats are more sensitive than WT rats to the LORR induced by isoflurane and ethanol. Moreover, isoflurane exposure induced a greater reduction in c-Fos expression in cerebellum granule cells of Gabra6^100Q rats than WT rats. Conclusions: Based on these data, we speculate that cerebellum may be involved in the hypnosis induced by some general anesthetics and thus may represent a novel target of general anesthetics.