Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice

Anesth Analg. 2021 Apr 1;132(4):e50-e55. doi: 10.1213/ANE.0000000000005387.

Abstract

Many general anesthetics potentiate gamma-aminobutyric acid (GABA) A receptors but their neuroanatomic sites of action are less clear. GABAergic neurons in the rostromedial tegmental nucleus (RMTg) send inhibitory projections to multiple arousal-promoting nuclei, but the role of these neurons in modulating consciousness is unknown. In this study, designer receptors exclusively activated by designer drugs (DREADDs) were targeted to RMTg GABAergic neurons of Vgat-ires-Cre mice. DREADDs expression was found in the RMTg and other brainstem regions. Activation of these neurons decreased movement and exploratory behavior, impaired motor coordination, induced electroencephalogram (EEG) oscillations resembling nonrapid eye movement (NREM) sleep without loss of righting and reduced the dose requirement for sevoflurane-induced unconsciousness. These results suggest that GABAergic neurons in the RMTg and other brainstem regions promote sedation and facilitate sevoflurane-induced unconsciousness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Brain Stem / drug effects*
  • Brain Stem / metabolism
  • Brain Waves / drug effects
  • Consciousness / drug effects*
  • Exploratory Behavior / drug effects
  • Female
  • GABAergic Neurons / drug effects*
  • GABAergic Neurons / metabolism
  • Male
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Receptors, G-Protein-Coupled / metabolism*
  • Sevoflurane / pharmacology*
  • Sleep / drug effects*

Substances

  • Anesthetics, Inhalation
  • Receptors, G-Protein-Coupled
  • Sevoflurane