TOLERANCE OF MICE TO NITROUS-OXIDE

Abstract

Mice continuously exposed to a subanesthetic dose of N2O become tolerant to N2O, 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 2-3 wk. Mice exposed to 25% N2O for 3 wk do not develop tolerance. Mice exhibit a withdrawal syndrome when removed from the subanesthetic environment after exposure to 40-70% but not 25% N2O for 3 wk. Tolerance to 50 or 70% N2O develops within 1 wk and is maximal at 2 wk. Tolerance to N2O 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.