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

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

Nelson, L. E., Guo, T. Z., Lu, J., Saper, C. B., Franks, N. P., Maze, M.·2002·Nature Neuroscience

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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  • The shared circuits hypothesis between sleep and anesthesia has been replicated across invertebrates to mammals.

    “This shared circuits hypothesis has been replicated across divergent species spanning invertebrates to mammals [54, 58, 82, 98, 99, 101].”

    From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]

  • Except for ketamine, systemic hypnotic doses of every general anesthetic examined recruit sleep-promoting VLPO neurons.

    “with the exception of ketamine, systemic delivery of hypnotic doses of every general anesthetic examined recruits sleep-promoting neurons in the VLPO [98–102]”

    From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]

  • VLPO metabolic activation, measured by c-Fos, is associated with various sedative-hypnotic drugs.

    “identified the metabolic activation of VLPO—as determined by c-Fos expression, a marker of antecedent cellular activity—in association with a variety of sedative-hypnotic drugs [98–100].”

    From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]

  • Using c-Fos as a proxy, neurons in many wake-promoting nuclei are inhibited during general anesthesia.

    “using c-Fos as a proxy for antecedent activity, neurons within many of these nuclei have been identified to be inhibited during general anesthesia [98, 100, 101, 114].”

    From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [98]

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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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