TOLERANCE TO OPIOID NARCOTICS. I. TOLERANCE TO THE "RUNNING FIT" CAUSED BY LEVORPHANOL IN THE MOUSE

The running fit induced by opioid narcotics in mice serves as a convenient graded measure of the effect of these drugs and a high degree of stereospecificity has been demonstrated by using D(—)-levorphanol and its L(+)-isomer.

Abstract

The running fit induced by opioid narcotics in mice serves as a convenient graded measure of the effect of these drugs. It is at least as sensitive a measure as analgesia. By using D(—)-levorphanol and its L(+)-isomer, a high degree of stereospecificity has been demonstrated. A number of criteria have been applied to show that the running fit is a typical pharmacologic effect of this family of drugs. The development of tolerance has been studied with repeated injections of levorphanol, and the loss of tolerance has been studied upon discontinuance of the drug. The rate of onset of tolerance and the degree of tolerance eventually attained are determined by the frequency of administration of a constant drug dose or by the size of the dose at a fixed interval. The duration of drug administration is irrelevant. Tolerance is reversible at a rate roughly the same as the rate of onset, and recovery of sensitivity to levorphanol is complete. Subsequent cycles of onset and offset of tolerance are indistinguishable from the first.