Propofol anaesthesia in mice is potentiated by muscimol and reversed by bicuculline

We have examined the role of gamma-aminobutyric acid (GABA) neurones in propofol anaesthesia in mice using the righting reflex. Propofol i.p. increased the percentage of loss of the righting reflex in a dose-dependent manner with an ED50 value of 140 (95% confidence limits 123-160) mg kg(-1) (n = 40; eight animals per dose, five doses per dose-response curve). The ED50 for propofol decreased significantly to 66 (58-75) mg kg(-1) in the presence of the GABA(A) receptor agonist muscimol 1 mg kg(-1) i.p. (n = 40) (P < 0.05). In contrast, the ED50 increased significantly to 240 (211-274) mg kg(-1) in the presence of the antagonist bicuculline 5 mg kg(-1) i.p. (n = 40) (P < 0.05). Our results suggest that propofol anaesthesia may be mediated, at least in part, by GABA neurones.