Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia
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Background: Methylphenidate or a D1 dopamine receptor agonist induces reanimation (active emergence) from general anesthesia. The authors tested whether electrical stimulation of dopaminergic nuclei also induces reanimation from general anesthesia. Methods: In adult rats, a bipolar insulated stainless steel electrode was placed in the ventral tegmental area (VTA, n = 5) or substantia nigra (n = 5). After a minimum 7-day recovery period, the isoflurane dose sufficient to maintain loss of righting was established. Electrical stimulation was initiated and increased in intensity every 3 min to a maximum of 120 µA. If stimulation restored the righting reflex, an additional experiment was performed at least 3 days later during continuous propofol anesthesia. Histological analysis was conducted to identify the location of the electrode tip. In separate experiments, stimulation was performed in the prone position during general anesthesia with isoflurane or propofol, and the electroencephalogram was recorded. Results: To maintain loss of righting, the dose of isoflurane was 0.9% ± 0.1 vol%, and the target plasma dose of propofol was 4.4 ± 1.1 µg/ml (mean ± SD). In all rats with VTA electrodes, electrical stimulation induced a graded arousal response including righting that increased with current intensity. VTA stimulation induced a shift in electroencephalogram peak power from δ (<4 Hz) to θ (4–8 Hz). In all rats with substantia nigra electrodes, stimulation did not elicit an arousal response or significant electroencephalogram changes. Conclusions: Electrical stimulation of the VTA, but not the substantia nigra, induces reanimation during general anesthesia with isoflurane or propofol. These results are consistent with the hypothesis that dopamine release by VTA neurons, but not substantia nigra neurons, induces reanimation from general anesthesia.
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Causal reactivation of some wake-promoting neurons during emergence has been explored with electrical, optogenetic, and chemogenetic methods in rodents and suggested in humans.
“the causal reactivation of some wake-promoting neurons during emergence from the anesthetic state has been explored using approaches such as electrical stimulation, optogenetics, and chemogenetics [115–118] in rodents and suggested in humans [119].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [117]
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- Authors
- Solt, K., Van Dort, C. J., Chemali, J. J., Taylor, N. E., Kenny, J. D., & Brown, E. N.
- Affiliations
- Harvard University (US)
- American Society of Anesthesiologists (US)
- Corresponding author
- Solt, Ken
- Venue
- Anesthesiology
- Published
- 2014-08
- Volume
- 121
- Issue
- 2
- Pages
- 311-319
- ISSN
- 0003-3022 (ISSN-L)
- PMC
- PMC4112744
- OpenAlex
- W1967982683
- Cited by
- 156
- References
- 40
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 19 · 2023: 11 · 2022: 12 · 2021: 26 · 2020: 14 · 2019: 13 · 2018: 8 · 2017: 6 · 2016: 10 · 2015: 10 · 2014: 6
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- National Institutes of Health (DP1OD003646)
- National Institute of General Medical Sciences (R01GM104948, TR01-GM104948, K08GM094394, T32GM007592)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- electrical stimulation, ventral tegmental area, substantia nigra, emergence from anesthesia, dopamine release, isoflurane, propofol, arousal, EEG
- MeSH terms
- Anesthesia Recovery Period, Anesthesia, General, Anesthesia, Intravenous, Animals, Arousal, Dopamine, Electric Stimulation, Electrodes, Implanted, Electroencephalography, Male, Receptors, Dopamine, Reflex, Substantia Nigra, Propofol, Rats, Sprague-Dawley, Ventral Tegmental Area, Anesthetics, Intravenous, Rats
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