Isoflurane-induced surgical tolerance mediated only in part by β3-containing GABA_A receptors

The targets which mediate the actions of the volatile general anaesthetic isoflurane are unknown. Based on pharmacological studies using GABA_A receptor antagonists it has recently been suggested that GABA_A receptors would not mediate the immobilizing action of isoflurane. Using the β3(N265M) knock-in mouse model we found that the mutant mice were less sensitive to the immobilizing action of isoflurane, indicating a role of β3-containing GABA_A receptors in mediating immobility. At high concentrations isoflurane also immobilizes β3(N265M) mice, indicating that other targets also mediate immobility. Thus, our findings support a multisite model for the immobilizing action of isoflurane.