Abstract

The development of tolerance to and physical dependence on morphine was quantitatively examined in rats implanted s. c. with 75-mg morphine pellets. The animals were maintained for up to seven days after pellet implantation and tolerance and physical dependence were assessed at daily intervals. Both tolerance and dependence peaked after three days of pellet implantation and then declined gradually after this time. The withdrawal reaction precipitated by naloxone in morphine-dependent rats was characterized by lacrimation, salivation, an ejaculate-like discharge, diarrhea, hyperactivity and most notably by wet-dog shakes. Since the observed withdrawal synsdrome included virtually every response which had previously been associated with morphine abstinence in the rat, it appears that morphine pellet implantation produces a degree of physical dependence which is at least as great as that which can be obtained with more commonly used techniques. On the basis of these data, it was concluded that the technique of pellet implantation can be used in the rat as a rapid and reliable means of producing a high degree of toleranuce and physical dependence on morphine which are readily quantifiable.