Propofol-induced anesthesia in mice is mediated by gamma-aminobutyric acid-A and excitatory amino acid receptors.
To elucidate the role of gamma-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 GABA(A) receptor agonist muscimol potentiated propofol (140 mg/kg; 50% effective dose for loss of righting reflex) induced anesthesia. Similarly, the benzodiazepine receptor agonist diazepam and the NMDA receptor antagonist MK-801 augmented propofol anesthesia, but the non-NMDA receptor antagonist CNQX did not. In contrast, the GABA(A) 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 GABA(A) and excitatory amino acid receptors.


CONCLUSIONS
We examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol-induced anesthesia in mice. The results suggest that propofol anesthesia is mediated, at least in part, by both GABA(A) and excitatory amino acid receptors.
Irifune
Masahiro
M
Departments of *Anesthesiology and †Pharmacology, Hiroshima University School of Dentistry, Hiroshima, Japan.
Takarada
Tohru
T
Shimizu
Yoshitaka
Y
Endo
Chie
C
Katayama
Sohtaro
S
Dohi
Toshihiro
T
Kawahara
Michio
M
D000768:Anesthesia, General; D018686:Anesthetics, Intravenous; D000818:Animals; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D015742:Propofol; D018079:Receptors, GABA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018686:Anesthetics, Intravenous; D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D015742:Propofol