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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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Citations
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Self-citationc-Fos and Related Immediate Early Gene Products as Markers of Activity in Neuroendocrine Systems
Hoffman, G. E., Smith, M. S., & Verbalis, J. G. (1993) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1993.1006 · Cited by 715
Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin
Jevtović‐Todorović, V., Todorovć, S. M., Mennerick, S. J., Powell, S., Dikranian, K. T., Benshoff, N. D., Zorumski, C. F., & Olney, J. W. (1998) · Nature Medicine · doi:10.1038/nm0498-460 · Cited by 675
How does xenon produce anaesthesia?
Franks, N. P., Dickinson, R., de Sousa, S. L. M., Hall, A. C., & Lieb, W. R. (1998) · Nature · doi:10.1038/24525 · Cited by 514
Self-citationIdentification of sleep-promoting neurons in vitro
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Pandharipande, P. P., Pun, B. T., Herr, D., Maze, M., Girard, T. D., Miller, R. R., Shintani, A., Thompson, J. L., Jackson, J. C., Deppen, S. A., et al. (2007) · JAMA · doi:10.1001/jama.298.22.2644 · Cited by 1,456
Self-citationGeneral Anesthesia, Sleep, and Coma
Brown, E. N., Lydic, R., & Schiff, N. D. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0808281 · Cited by 1,413
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
Franks, N. P. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2372 · Cited by 1,295
Self-citationHistamine in the Nervous System
Haas, H. L., Sergeeva, O. A., & Selbach, O. (2008) · Physiological Reviews · doi:10.1152/physrev.00043.2007 · Cited by 1,251
The role of histamine and the tuberomamillary nucleus in the nervous system
Haas, H., & Panula, P. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1034 · Cited by 929
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
- Licence
- www.springer.com/tdm (tdm)
- 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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