Single-dose tolerance to morphine hypothermia in the rat: differentiation of acute from long-term tolerance.
The time course for the development and disappearance fo tolerance to the hypothermic effects of morphine was determined after a single subcutaneous injection (10 mg/kg) in rats. Body temperature responses to second injections, given at varying times after the first, were compared with those produced by the initial injections. Tolerance (attenuation of the hypothermic response) induced by a single dose of morphine was found to be biphasic. Acute tolerance was apparent by 4.5 hours and lasted at least 20 hours after morphine administration. Development of long-term tolerance occurred within 24 hours, 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 hours after morphine. Long-term tolerance was attenuated by co-administration of naloxone with initial dose of morphine. Long-term tolerance induced by multiple doses of morphine (300 mg/kg/day) differed from that induced by a single dose in persistence (3-4 weeks) rather than in quality or magnitude. The thermoregulatory response of the rat provides a sensitive measurement system which allows discrimination between acute and long-term opiate effects.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003864:Depression, Chemical; D004347:Drug Interactions; D004361:Drug Tolerance; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology; D013997:Time Factors
D011957:Receptors, Opioid; D009020:Morphine; D010424:Pentobarbital