VOLATILE ANESTHETIC REQUIREMENTS DIFFER IN MICE SELECTIVELY BRED FOR SENSITIVITY OR RESISTANCE TO DIAZEPAM - IMPLICATIONS FOR THE SITE OF ANESTHESIA

One approach to elucidating the general anesthetic target has used gen etic selection procedures, wherein animals are bred for sensitivity or resistance to general anesthetics and correlations are sought with a specific neuronal structural or functional defect. For example, murine strains have been developed that are either sensitive or resistant to the obtunding effects of diazepam, as assessed by their ability to ma intain balance on a rotating rod. The present study explored whether d iazepam-sensitive (DS) and diazepam-resistant (DR) mice might also be similarly divergent in the obtunding response to general anesthetics, by testing the requirements for halothane and enflurane in these strai ns. Using a carousel enclosed in a chamber, the end-point of loss-of-r ighting reflex was defined. For both anesthetics, the DS group had a l ower median effective dose (ED50, %atm) than did the DR group, and the reductions paralleled diazepam susceptibility. For example, with halo thane, the ED50 for the DS group was 0.72 +/- 0.022 (SE); the ED50 for the DR group was 0.87 +/- 0.030 (P < 0.0001). Similar results were ob tained with enflurane. Such findings associate an inbred difference in response to diazepam with altered volatile anesthetic requirement, su ggesting that these two phenotypes are mediated by a common underlying mechanism.