Tolerance to Nitrous Oxide Analgesia in Rats and Mice

Abstract

The nature of tolerance to the analgesic action of N2O was characterized. Analgesia was assessed in rats using a tail-flick latency test and in mice using an abdominal constriction test. Rats and mice were exposed to N2O, 75%, the balance O2, continuously for 16-18 h. On re-exposure to N2O 30 min later, these animals were found tolerant to N2O in that the analgesic response was decreased by at least 50%. Animals tolerant to N2O were not tolerant to morphine. Morphine (0.25-1.5 mg/kg) produced equal degrees of analgesia in control and N2O-tolerant mice and rats. Rats made tolerant to morphine by repeated daily injections of as much as 400 mg/kg s.c. or by s.c. implantation of morphine pellets (75 mg, twice) showed a decreased analgesic response to N2O. The cross-tolerance between N2O and morphine appears unique in that it is unidirectional.