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

Neurosci Lett. 2021 Sep 25:762:136142. doi: 10.1016/j.neulet.2021.136142. Epub 2021 Jul 29.

Abstract

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. Gabra6100Q allele Sprague-Dawley (SD) rats have a naturally occurring single nucleotide polymorphism in the GABAA 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 Gabra6100Q 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: Gabra6100Q 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 Gabra6100Q 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.

Keywords: Cerebellum; GABA(A) Receptor a6 subunit; General anesthetics; Loss of consciousness; Loss of righting reflex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Central Nervous System Depressants / pharmacology
  • Cerebellum / drug effects*
  • Ethanol / pharmacology*
  • Isoflurane / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / genetics*
  • Reflex, Righting / drug effects
  • Unconsciousness / chemically induced
  • Unconsciousness / genetics*

Substances

  • Anesthetics, Inhalation
  • Central Nervous System Depressants
  • Gabra6 protein, rat
  • Receptors, GABA-A
  • Ethanol
  • Isoflurane