Cited by 568Anesthesia and Sedative AgentsSleep and Wakefulness ResearchNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.

The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway

Abstract

We investigated the role of regionally discrete GABA (gamma-aminobutyric acid) receptors in the sedative response to pharmacological agents that act on GABA(A) receptors (muscimol, propofol and pentobarbital; 'GABAergic agents') and to ketamine, a general anesthetic that does not affect GABA(A) receptors. Behavioral studies in rats showed that the sedative response to centrally administered GABAergic agents was attenuated by the GABA(A) receptor antagonist gabazine (systemically administered). The sedative response to ketamine, by contrast, was unaffected by gabazine. Using c-Fos as a marker of neuronal activation, we identified a possible role for the tuberomammillary nucleus (TMN): when gabazine was microinjected directly into the TMN, it attenuated the sedative response to GABAergic agents. Furthermore, the GABA(A) receptor agonist muscimol produced a dose-dependent sedation when it was administered into the TMN. We conclude that the TMN is a discrete neural locus that has a key role in the sedative response to GABAergic anesthetics.

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Crossref · 10.1038/nn913

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Metadata

Authors
Nelson, L. E., Guo, T. Z., Lu, J., Saper, C. B., Franks, N. P., & Maze, M.
Affiliations
  • Chelsea and Westminster Hospital (GB)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Franks, N. P.
Venue
Nature Neuroscience
Published
2002-08-26
Volume
5
Issue
10
Pages
979-984
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2074671627
Cited by
568
References
47
Citations by year
2026: 6 · 2025: 18 · 2024: 20 · 2023: 23 · 2022: 11 · 2021: 18 · 2020: 19 · 2019: 16 · 2018: 21 · 2017: 26 · 2016: 26 · 2015: 17 · 2014: 36 · 2013: 18 · 2012: 27
FWCI
25.82
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Medical Research Council
  • National Institute on Aging (AG09975, P01AG009975)
  • National Heart, Lung, and Blood Institute (HL 60292, P50HL060292)
Topics
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
GABAA receptor, sedation, anesthesia, tuberomammillary nucleus, gabazine, muscimol, propofol, pentobarbital, ketamine, c-fos, sleep regulation, neuronal activation
MeSH terms
Anesthesia, Anesthetics, Animals, Hypnotics and Sedatives, Hypothalamic Area, Lateral, Male, Neural Pathways, Rats, Inbred F344, Receptors, GABA-A, Sleep, GABA Agonists, GABA Antagonists, Rats, GABA-A Receptor Agonists, GABA-A Receptor Antagonists

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