STUDIES ON PHYSICAL DEPENDENCE INDUCIBLE BY HOURS EXPOSURE OF MICE TO MORPHINE

Abstract

Long exposure to morphine or its surrogates to humans inevitably results in an intoxicated state which is characterized by two types of morbid phenomena, tolerance and dependence. This state is fully or partially reproducible in some species of laboratory mammals and forms a basis to explore the mechanisms underlying those symptoms and also to screenm orphine-like untoward properties of newly developed analgesics in laboratory level.
Recently, Maggiolo and Huidobro (1, 2) have defined abstinence syndrome in morphinepellet implanted mice. Later, using jumping response as a criterion, Way et al. (3) attempted to quantify the degree of physical dependence, thus adding this animal species to the list of animal models usable in this research field. Further, the utilization of mice seems to have been confirmed in more recent experiments by Cheney and Goldstein (4) and Saelens et al. (5).
In previous papers (6, 7), it was reported that continuous infusion of morphine could develop tolerance in mice as early as a few hours and that concomitant development of physical dependence was detected by the precipitation of abstinence signs with naloxone. To the present, various techniques have been developed in order to morphinize the laboratory animals and, according to the conditions employed, obtained tolerance or dependence differed in degree one from another, however, it is not yet known whether or not their properties also differ. Thus, using various techniques we investigated how rapidly in terms of hour(s) the animal could become sensitive to naloxone, namely physically dependent, and in what aspects the rapidly inducible type of dependence would differ from that after long exposure to morphine.