Potencies of Inhaled Anesthetics and Alcohol in Mice Selectively Bred for Resistance and Susceptibility to Nitrous

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Abstract
A selective breeding process designed to produce mice resistant (HI mice) and susceptible (LO mice) to N2O anesthesia was continued through 10 generations. At the 10 generation, the N2O requirements of the HI and LO mice (as measured by the partial pressure of N2O required to abolish the righting reflex) were separated by > 0.7 atm. The HI mice also had a higher anesthetic requirement for cyclopropane, enflurane, isoflurane, halothane and methoxyflurane, as measured by response to a tail-clamp stimulus. HI mice given an i.p. ethanol (4 g/kg) had 44% shorter sleep times and 12% higher blood alcohol levels upon awakening than did LO mice. For N, Ar, cyclopropane, isoflurane, enflurane, halothane and methoxyflurane, the doses at which the righting reflex was abolished in HI and LO mice were determined. The separation in righting-reflex ED50 between these 2 lines was inversely related to the lipid solubility of the anesthetic. For the most lipid-soluble anesthetic, methoxyflurane, no significant differences in potency, as measured by the righting-reflex ED50, could be detected between the HI and LO mice. The separation in anesthetic requirements, as measured by the tail-clamp ED50, was approximately the same for each of the anesthetics tested.