The sensitivity of drugs towards the respective residues βM2-15’ in β2- and β3-containing receptors led to the production of knock-in mice which exhibited a reduced sensitivity to the sedative (β2N265S: Reynolds et al., 2003) and anesthetic actions of etomidate in vivo (β3N265M: Jurd et al., 2003). These studies demonstrated not only that GABAA-Rs mediate the action of the general anesthetic etomidate, but also that the behavioral effects depend differentially on β2- or β3-containing GABAA-R, presumably due to their anatomical localization in brain structures contributing to the respective actions.
