TY - JOUR
T1 - Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice
AU - Sugimura, Mitsutaka
AU - Kitayama, Shigeo
AU - Morita, Katsuya
AU - Imai, Yasuo
AU - Irifune, Masahiro
AU - Takarada, Tohru
AU - Kawahara, Michio
AU - Dohi, Toshihiro
N1 - Funding Information:
This study was supported, in part, by the Grant-in-Aid for Scientific Research from Ministry of Education, Science, and Culture, Japan. The gift of baclofen from Ciba-Geigy Novartis, Japan is gratefully acknowledged.
PY - 2002
Y1 - 2002
N2 - The effects of γ-aminobutyric acid (GABA) receptor modulators and GABA uptake inhibitors on volatile and intravenous anesthetic-induced anesthesia were examined in male ICR mice, as assessed by the loss of righting reflex (LORR). The GABA uptake inhibitors, NO-711 and SKF89976A, which are permeable to the blood-brain barrier (BBB), but not nipecotic acid or guvacine, which poorly permeate BBB, shortened the onset of LORR but did not affect the duration of LORR induced by 1.5% halothane and 2% isoflurane. NO-711 and SKF89976A shortened the onset of and prolonged the duration of LORR induced by thiamylal (45 mg/kg ip). The GABA mimetics, muscimol and diazepam, shortened the onset of and prolonged the duration of LORR induced by halothane, isoflurane, and thiamylal. On the other hand, picrotoxin, a GABAA receptor antagonist, prolonged the onset of LORR induced by all anesthetics tested. Another GABAA receptor antagonist, bicuculline, prolonged the onset of LORR induced by halothane, but not by isoflurane or thiamylal. Both antagonists failed to affect the duration of LORR induced by halothane, isoflurane, or thiamylal. Baclofen, a GABAB receptor agonist, enhanced both volatile anesthetics- and thiamylal-induced anesthesia. These results suggest that anesthesia induced by volatile and intravenous anesthetics might be correlated with the modification of the pre- and/or postsynaptic GABAergic activities.
AB - The effects of γ-aminobutyric acid (GABA) receptor modulators and GABA uptake inhibitors on volatile and intravenous anesthetic-induced anesthesia were examined in male ICR mice, as assessed by the loss of righting reflex (LORR). The GABA uptake inhibitors, NO-711 and SKF89976A, which are permeable to the blood-brain barrier (BBB), but not nipecotic acid or guvacine, which poorly permeate BBB, shortened the onset of LORR but did not affect the duration of LORR induced by 1.5% halothane and 2% isoflurane. NO-711 and SKF89976A shortened the onset of and prolonged the duration of LORR induced by thiamylal (45 mg/kg ip). The GABA mimetics, muscimol and diazepam, shortened the onset of and prolonged the duration of LORR induced by halothane, isoflurane, and thiamylal. On the other hand, picrotoxin, a GABAA receptor antagonist, prolonged the onset of LORR induced by all anesthetics tested. Another GABAA receptor antagonist, bicuculline, prolonged the onset of LORR induced by halothane, but not by isoflurane or thiamylal. Both antagonists failed to affect the duration of LORR induced by halothane, isoflurane, or thiamylal. Baclofen, a GABAB receptor agonist, enhanced both volatile anesthetics- and thiamylal-induced anesthesia. These results suggest that anesthesia induced by volatile and intravenous anesthetics might be correlated with the modification of the pre- and/or postsynaptic GABAergic activities.
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U2 - 10.1016/S0091-3057(01)00728-6
DO - 10.1016/S0091-3057(01)00728-6
M3 - Article
C2 - 11900777
AN - SCOPUS:0036210008
SN - 0091-3057
VL - 72
SP - 111
EP - 116
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 1-2
ER -