SINGLE-DOSE TOLERANCE TO MORPHINE HYPOTHERMIA IN RAT - DIFFERENTIATION OF ACUTE FROM LONG-TERM TOLERANCE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 202  (3) , 654-659
Abstract
The time course for the development and disappearance of tolerance to the hypothermic morphine effects was determined after a single s.c. injection (10 mg/kg) in rats. Body temperature responses to 2nd injections, given at varying times after the 1st, were compared with those produced by the initial injections. Tolerance (attenuation of the hypothermic response) induced by a single morphine dose was biphasic. Acute tolerance was apparent by 4.5 h and lasted at least 20 h after morphine administration. Development of long-term tolerance occurred within 24 h, was maximal at 3 days and persisted up to 11 days. Both acute and long-term tolerance were drug specific since hypothermic responses to pentobarbital were not altered either 4.5 or 72 h after morphine. Long-term tolerance was attenuated by co-administration of naloxone with the initial morphine dose. Long-term tolerance induced by multiple morphine doses (300 mg/kg per day) differed from that induced by a single dose in persistence (3-4 wk) rather than in quality or magnitude. The rat thermoregulatory response provides a sensitive measurement system which allows discrimination between acute and long-term opiate effects.