DEVELOPMENT AND LOSS OF TOLERANCE TO MORPHINE IN THE RAT AFTER SINGLE AND MULTIPLE INJECTIONS

Tolerance to the drug effect developed in a parallel fashion for both measures and return of drug sensitivity, however, was much more rapid with swimming than with the response to heat.

Abstract

The development and loss of tolerance in the rat to the effects of morphine on two measures of response, reaction to a noxious stimulus (heat)and speed of swimming, were studied. Tolerance to the drug effect developed in a parallel fashion for both measures. Return of drug sensitivity, however, was much more rapid with swimming than with the response to heat. The degree of tolerance achieved, as measured by the hot plate, was the same when animals were given 100 mg/kg of morphine sulfate twice daily for 50 days or 20 mg/kg seven times at irregular intervals. This effect of a relatively few irregularly spaced injections in producing a profound degree of tolerance was not seen when speed of swimming was used as a measure of response to drug. Complete recovery of drug sensitivity after a course of chronic morphine administration does not occur for at least 9 months as measured by swimming and more than 12 months as tested by the hot plate. The effects of a single injection of 20 mg/kg of morphine sulfate can be observed for at least a year using the hot plate as a test of drug response. No effects of a single previous injection of morphine sulfate can be detected using speed of swimming as the response measured.