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

The targets which mediate the actions of the volatile general anaesthetic isoflurane are unknown. Based on pharmacological studies using GABAA receptor antagonists it has recently been suggested that GABAA 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 GABAA 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.