ArticleKoblin DD, Dong DE, Eger EI.
J Pharmacol Exp Ther. 1979 Nov;211(2):317-25.
Mice continuously exposed to a subanesthetic dose of nitrous oxide (N2O) become tolerant to nitrous oxide, as measured by an increase in their ED50 (dose required to abolish the righting reflex in 50% of animals) for N2O. The maximum increase in ED50 is approximately 0.25 atm for mice exposed to 40, 50 or 70% N2O for 2 to 3 weeks. Mice exposed to 25% N2O for 3 weeks do not develop tolerance. Mice exhibit a withdrawal syndrome when removed from the subanesthetic environment after exposure to 40 to 70% but not 25% N2O for 3 weeks. Tolerance to 50 or 70% N2O develops within 1 week and is maximal at 2 weeks. Tolerance to nitrous oxide is lost within 6 days following removal of the animals from the subanesthetic environment. Synaptic membrane fatty acid, phospholipid, and cholesterol compositions of tolerant animals are not significantly altered.