| Gamma-aminobutyric acid-mediated neurotransmission in the pontine reticular formation modulates hypnosis, immobility, and breathing during isoflurane anesthesia. | |
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MedLine Citation:
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PMID: 19034094 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Many general anesthetics are thought to produce a loss of wakefulness, in part, by enhancing gamma-aminobutyric acid (GABA) neurotransmission. However, GABAergic neurotransmission in the pontine reticular formation promotes wakefulness. This study tested the hypotheses that (1) relative to wakefulness, isoflurane decreases GABA levels in the pontine reticular formation; and (2) pontine reticular formation administration of drugs that increase or decrease GABA levels increases or decreases, respectively, isoflurane induction time. METHODS: To test hypothesis 1, cats (n = 5) received a craniotomy and permanent electrodes for recording the electroencephalogram and electromyogram. Dialysis samples were collected from the pontine reticular formation during isoflurane anesthesia and wakefulness. GABA levels were quantified using high-performance liquid chromatography. For hypothesis 2, rats (n = 10) were implanted with a guide cannula aimed for the pontine reticular formation. Each rat received microinjections of Ringer's (vehicle control), the GABA uptake inhibitor nipecotic acid, and the GABA synthesis inhibitor 3-mercaptopropionic acid. Rats were then anesthetized with isoflurane, and induction time was quantified as loss of righting reflex. Breathing rate was also measured. RESULTS: Relative to wakefulness, GABA levels were significantly decreased by isoflurane. Increased power in the electroencephalogram and decreased activity in the electromyogram caused by isoflurane covaried with pontine reticular formation GABA levels. Nipecotic acid and 3-mercaptopropionic acid significantly increased and decreased, respectively, isoflurane induction time. Nipecotic acid also increased breathing rate. CONCLUSION: Decreasing pontine reticular formation GABA levels comprises one mechanism by which isoflurane causes loss of consciousness, altered cortical excitability, muscular hypotonia, and decreased respiratory rate. |
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Authors:
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Giancarlo Vanini; Christopher J Watson; Ralph Lydic; Helen A Baghdoyan |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 109 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-26 Completed Date: 2008-12-24 Revised Date: 2012-05-02 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 978-88 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anesthesia
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methods* Anesthetics, Inhalation / pharmacology Animals Cats Immobility Response, Tonic / drug effects, physiology* Isoflurane / pharmacology* Male Pons / drug effects, physiology Rats Rats, Sprague-Dawley Respiration* / drug effects Reticular Formation / drug effects, physiology* Synaptic Transmission / drug effects, physiology gamma-Aminobutyric Acid / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL40881/HL/NHLBI NIH HHS; HL57120/HL/NHLBI NIH HHS; HL65272/HL/NHLBI NIH HHS; MH45361/MH/NIMH NIH HHS; R01 HL040881/HL/NHLBI NIH HHS; R01 HL040881-20/HL/NHLBI NIH HHS; R01 HL057120-10/HL/NHLBI NIH HHS; R01 HL065272-08/HL/NHLBI NIH HHS; R37 MH045361-22/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Inhalation; 26675-46-7/Isoflurane; 56-12-2/gamma-Aminobutyric Acid |
| Comments/Corrections | |
Comment In:
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Anesthesiology. 2008 Dec;109(6):948-50
[PMID:
19034087
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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