Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice

The effects of gamma-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 i.p.). 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.