Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat.

Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Research Abstract Details 

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Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Abstract Text:

BACKGROUND: Neuronal nicotinic acetylcholine receptors are both potently inhibited by anesthetics and densely expressed in the thalamus. Brain imaging shows that thalamic activity suppression accompanies anesthetic-induced unconsciousness. Therefore, anesthetic-induced unconsciousness may involve direct antagonism of thalamic nicotinic receptors. The authors test this by separately attempting to block or enhance anesthetic-induced loss of righting in rats using intrathalamic microinjections of nicotine or its antagonist. METHODS: Rats were implanted with a cannula aimed at the thalamus or control locations. A week later, loss of righting was induced using sevoflurane (1.4 +/- 0.2%). A dose-parameter study (n = 35) first identified an optimal intrathalamic nicotine dose associated with arousal. Subsequently, this dose was used to pinpoint the thalamic site mediating the arousal response (n = 107). Finally, sevoflurane righting dose and response specificity were assessed after blocking nicotinic channels with intrathalamic mecamylamine pretreatment (n = 8) before nicotine challenge. RESULTS: Nicotine (150 microg/0.5 microl over 1 min) was the optimal arousal dose, because lower doses (75 microg) were ineffective and higher doses (300 microg) often caused seizures. Nicotine temporarily restored righting and mobility in animals when microinjections involved the central medial thalamus (P < 0.0001, chi-square). Righting occurred despite continued sevoflurane administration. Intrathalamic mecamylamine pretreatment did not lower the sevoflurane dose associated with loss of righting, but prevented the nicotine arousal response. CONCLUSIONS: The reversal of unconsciousness found here with intrathalamic microinfusion of nicotine suggests that suppression of the midline thalamic cholinergic arousal system is part of the mechanism by which anesthetics produce unconsciousness.

Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Publishing Authors By Initials

For similar nervous system: central nervous system: brain: prosencephalon: diencephalon: thalamus research abstracts see: nervous system: central nervous system: brain: prosencephalon: diencephalon: thalamus research

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Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Anesthesiology

VOLUME: 107

Page Numbers: 264-72

Journal Abbreviation: Anesthesiology

ISSN: 0003-3022

DAY: 3

MONTH: Aug

YEAR: 2007

Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 1300217

Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Keywords Mesh Terms:

KEYWORDS: Thalamus

MESH TERMS: drug effects

Chemical & Substance for Abstract: Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Information

Substance Name: Mecamylamine

Registry Number: 60-40-2

Grant and Affiliation Information for Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat.

AFFILIATION: Department of Anesthesiology, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R01-NS65212

ACRONYM: NS

MEDLINETA: Anesthesiology

REFSOURCE: Anesthesiology. 2007 Aug;107(2):195-8

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