TOLERANCE TO AND PHYSICAL DEPENDENCE ON MORPHINE IN RATS.

Abstract

The effects of large doses of morphine in nontolerant and tolerant rats as well as the effects of abruptly withdrawing morphine in rats experimentally addicted to large doses of morphine have been studied on body weight, temperature, metabolic rate, respiratory rate, water consumption and various forms of motor activity and behavior. In confirmation of many early reports, tolerance develops to certain depressant actions of large doses of morphine and the effects of morphine in the tolerant rat are primarily excitatory, consisting of an increase in body temperature, metabolic rate and motor activity. The abstinence syndrome of rats addicted to large doses of morphine seems to have two phases: (1) An early phase, which has been called “primary abstinence” consists of weight loss, an increased number of “wet dog” shakes, increased activity, and a fall in body temperature and metabolic rate. The primary abstinence syndrome becomes clearly manifest within 8 to 16 hours following the last dose of morphine and persists for approximately 72 hours. (2) The secondary abstinence syndrome emerges thereafter and consists of a rapid gain in body weight, elevated body temperature and metabolic rate and an increase in water consumption. The secondary abstinence syndrome is protracted and small differences have been seen between addicted and control animals as long as four to six months after withdrawal of morphine.