Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice.
Anesthetics, Inhalation
/ pharmacology
Animals
Behavior, Animal
/ drug effects
Brain Stem
/ drug effects
Brain Waves
/ drug effects
Consciousness
/ drug effects
Exploratory Behavior
/ drug effects
Female
GABAergic Neurons
/ drug effects
Male
Mice, Transgenic
Motor Activity
/ drug effects
Receptors, G-Protein-Coupled
/ metabolism
Sevoflurane
/ pharmacology
Sleep
/ drug effects
Journal
Anesthesia and analgesia
ISSN: 1526-7598
Titre abrégé: Anesth Analg
Pays: United States
ID NLM: 1310650
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
pubmed:
10
2
2021
medline:
7
4
2021
entrez:
9
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33560660
doi: 10.1213/ANE.0000000000005387
pii: 00000539-202104000-00031
pmc: PMC7969415
mid: NIHMS1654437
doi:
Substances chimiques
Anesthetics, Inhalation
0
Receptors, G-Protein-Coupled
0
Sevoflurane
38LVP0K73A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e50-e55Subventions
Organisme : NIGMS NIH HHS
ID : P01 GM118269
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM126155
Pays : United States
Informations de copyright
Copyright © 2021 International Anesthesia Research Society.
Déclaration de conflit d'intérêts
Conflicts of Interest: See Disclosures at the end of the article.
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