Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors

Hai T. Nguyen, Ke Yong Li, Ralph L. Dagraca, Ellise S. Delphin, Ming Xiong, Jiang H. Ye

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and absence of strychnine (a glycine receptor antagonist), GABAzine (a γ-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and γ-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. RESULTS: Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. In addition, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. CONCLUSION: Strychnine, the glycine receptor antagonist, dose-dependently reduced propofol-induced LORR in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis.

Original languageEnglish (US)
Pages (from-to)326-332
Number of pages7
JournalAnesthesiology
Volume110
Issue number2
DOIs
StatePublished - Feb 2009
Externally publishedYes

Fingerprint

Glycine Receptors
Hypnosis
Propofol
Righting Reflex
Strychnine
Brain
Aminobutyrates
Ketamine
Anesthetic Hypnosis
Glycine
Posterior Hypothalamus
Neurons
GABAergic Neurons
General Anesthetics
Glutamate Receptors
N-Methylaspartate
Hypnotics and Sedatives
Sleep
Central Nervous System

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors. / Nguyen, Hai T.; Li, Ke Yong; Dagraca, Ralph L.; Delphin, Ellise S.; Xiong, Ming; Ye, Jiang H.

In: Anesthesiology, Vol. 110, No. 2, 02.2009, p. 326-332.

Research output: Contribution to journalArticle

Nguyen, Hai T. ; Li, Ke Yong ; Dagraca, Ralph L. ; Delphin, Ellise S. ; Xiong, Ming ; Ye, Jiang H. / Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors. In: Anesthesiology. 2009 ; Vol. 110, No. 2. pp. 326-332.
@article{ce9f5cad7c1e45759eb45caf97d5b3a5,
title = "Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors",
abstract = "BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and absence of strychnine (a glycine receptor antagonist), GABAzine (a γ-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and γ-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. RESULTS: Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. In addition, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. CONCLUSION: Strychnine, the glycine receptor antagonist, dose-dependently reduced propofol-induced LORR in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis.",
author = "Nguyen, {Hai T.} and Li, {Ke Yong} and Dagraca, {Ralph L.} and Delphin, {Ellise S.} and Ming Xiong and Ye, {Jiang H.}",
year = "2009",
month = "2",
doi = "10.1097/ALN.0b013e3181942b5b",
language = "English (US)",
volume = "110",
pages = "326--332",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors

AU - Nguyen, Hai T.

AU - Li, Ke Yong

AU - Dagraca, Ralph L.

AU - Delphin, Ellise S.

AU - Xiong, Ming

AU - Ye, Jiang H.

PY - 2009/2

Y1 - 2009/2

N2 - BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and absence of strychnine (a glycine receptor antagonist), GABAzine (a γ-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and γ-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. RESULTS: Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. In addition, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. CONCLUSION: Strychnine, the glycine receptor antagonist, dose-dependently reduced propofol-induced LORR in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis.

AB - BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and absence of strychnine (a glycine receptor antagonist), GABAzine (a γ-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and γ-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. RESULTS: Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. In addition, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. CONCLUSION: Strychnine, the glycine receptor antagonist, dose-dependently reduced propofol-induced LORR in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis.

UR - http://www.scopus.com/inward/record.url?scp=61549110188&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61549110188&partnerID=8YFLogxK

U2 - 10.1097/ALN.0b013e3181942b5b

DO - 10.1097/ALN.0b013e3181942b5b

M3 - Article

C2 - 19194159

AN - SCOPUS:61549110188

VL - 110

SP - 326

EP - 332

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 2

ER -