Propofol-induced anesthesia in mice is mediated by γ-aminobutyric acid-A and excitatory amino acid receptors

Masahiro Irifune, Tohru Takarada, Yoshitaka Shimizu, Chie Endo, Sohtaro Katayama, Toshihiro Dohi, Michio Kawahara

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

To elucidate the role of γ-aminobutyric acid (GABA)A receptor complex and excitatory amino acid receptors (N-methyl-D-aspartate [NMDA] and non-NMDA receptors) in propofol-induced anesthesia, we examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol anesthesia in mice. All drugs were administered intraperitoneally. General anesthetic potencies were evaluated using a righting reflex assay. The GABAA receptor agonist muscimol potentiated propofol (140 mg/kg; 50% effective dose for loss of righting reflex) induced anesthesia. Similarly, the benzodiazepine receptor agonist diaze-pain and the NMDA receptor antagonist MK-801 augmented propofol anesthesia, but the non-NMDA receptor antagonist CNQX did not. In contrast, the GABAA receptor antagonist bicuculline antagonized propofol (200 mg/ kg; 95% effective dose for loss of righting reflex) induced anesthesia. However, neither the benzodiazepine receptor antagonist flumazenil, the GABA synthesis inhibitor L-allylglycine, nor the NMDA receptor agonist NMDA reversed propofol anesthesia. Conversely, the non-NMDA receptor agonist kainate enhanced propofol anesthesia. These results suggest that propofol-induced anesthesia is mediated, at least in part, by both GABAA and excitatory amino acid receptors.

Original languageEnglish
Pages (from-to)424-429
Number of pages6
JournalAnesthesia and Analgesia
Volume97
Issue number2
DOIs
Publication statusPublished - Aug 1 2003

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Aminobutyrates
Glutamate Receptors
Propofol
Anesthesia
Righting Reflex
D-Aspartic Acid
GABA-A Receptors
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Allylglycine
GABA Antagonists
GABA-A Receptor Agonists
6-Cyano-7-nitroquinoxaline-2,3-dione
GABA-A Receptor Antagonists
Flumazenil
General Anesthetics
Muscimol
Dizocilpine Maleate
Bicuculline
Kainic Acid

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Propofol-induced anesthesia in mice is mediated by γ-aminobutyric acid-A and excitatory amino acid receptors. / Irifune, Masahiro; Takarada, Tohru; Shimizu, Yoshitaka; Endo, Chie; Katayama, Sohtaro; Dohi, Toshihiro; Kawahara, Michio.

In: Anesthesia and Analgesia, Vol. 97, No. 2, 01.08.2003, p. 424-429.

Research output: Contribution to journalArticle

Irifune, Masahiro ; Takarada, Tohru ; Shimizu, Yoshitaka ; Endo, Chie ; Katayama, Sohtaro ; Dohi, Toshihiro ; Kawahara, Michio. / Propofol-induced anesthesia in mice is mediated by γ-aminobutyric acid-A and excitatory amino acid receptors. In: Anesthesia and Analgesia. 2003 ; Vol. 97, No. 2. pp. 424-429.
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