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ANESTHETIC PHARMACOLOGY

Propofol-Induced Anesthesia in Mice Is Mediated by -Aminobutyric Acid-A and Excitatory Amino Acid Receptors

Masahiro Irifune, DDS PhD^*, Tohru Takarada, DDS PhD^*, Yoshitaka Shimizu, DDS^*, Chie Endo, DDS^*, Sohtaro Katayama, DDS^*, Toshihiro Dohi, PhD, and Michio Kawahara, MD PhD^*

Departments of *Anesthesiology and Pharmacology, Hiroshima University School of Dentistry, Hiroshima, Japan

Address correspondence and reprint requests to Masahiro Irifune, DDS, PhD, Department of Anesthesiology, Hiroshima University School of Dentistry, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Address e-mail to mirifun{at}hiroshima-u.ac.jp

To elucidate the role of -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.

IMPLICATIONS: 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.

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