Tolerance to and Dependence on Inhalational Anesthetics

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Abstract
Mice continuously exposed to 50% N2O for 2-3 wk become tolerant to anesthesia, as evidenced by an increase in the concentration of N2O necessary to abolish the righting reflex from 1.49 .+-. 0.045 atm to 1.67 .+-. 0.053 atm after 3 wk (auto-tolerance). There was an increase in the concentration of a 2nd anesthetic (cyclopropane or isoflurane) necessary to abolish the righting reflex (cross-tolerance). Cyclopropane ED50 increased from 0.130 .+-. 0.0068 atm to 0.148 .+-. 0.0044 atm after 2 wk of exposure to 50%, N2O. Isoflurane ED50 increased from 0.00570 .+-. 0.000163 atm to 0.00622 .+-. 0.000200 atm after 3 wk of exposure to 50% N2O. Mice continuously exposed to isoflurane 0.15 or 0.3%, showed neither auto- nor cross-tolerance. After 3 wk of exposure 69% of mice removed from 50% N2O convulsed when suspended by the tail (i.e., manifested a stimulus-elicited withdrawal syndrome indicating dependence on N2O). After 3 wk of exposure 43% of mice convulsed when removed from 0.15% isoflurane. Only 4% of mice convulsed after 6 or 9 wk of exposure to this concentration of isoflurane.

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