Selective Breeding Alters Murine Resistance to Nitrous Oxide Without Alteration in Synaptic Membrane Lipid Composition

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Abstract
A normal population of mice was separated into 2 groups with reproducibly high (> 1.63 atm) or reproducibly low (< 1.29 atm) N2O requirements. Males and females with the reproducibly high anesthetic requirements were mated, as were males and females with the reproducibly low anesthetic requirements. The 1st-generation offspring from parents with the high anesthetic requirements had a higher N2O ED50 (concentration of N2O required to abolish the righting reflex in 1/2 of the animals) than did offspring from parents with the low anesthetic requirements. Mice with the lowest and the highest anesthetic requirements in the 1st generation were bred to give the 2nd generation. By repeating this process of breeding, N2O ED50 testing, and selection of mice with the highest and lowest anesthetic requirements through 5 generations, the authors were able to breed 2 groups of mice separated by approximately 0.5 atm in N2O requirements. This alteration in anesthetic requirement could not be explained by an altered synaptic membrane lipid composition, since no significant difference in synaptic membrane phospholipid, fatty acid, or cholesterol compositions could be detected in the 2 groups of mice with high and low anesthetic requirements.