Abstract

Experiments aimed at comparing acute and chronic tolerance to, as well as acute and chronic physical dependence on, morphine were conducted in both high (C5-C6) and low (T-10) chronic spinal dogs. Abstinence signs, precipitated by nalorphine, originating in both supraspinal portions of the nervous system as well as in spinal cord structures below the level of transection were studied. Acute physical dependence develops in the spinal cord; however, both acute tolerance and acute physical dependence develop more rapidly and more completely in supraspinal structures. The spinal cord has a capacity equal to or greater than that of supraspinal structures to develop chronic tolerance and physical dependence. These findings indicate that acute and chronic tolerance as well as acute and chronic physical dependence are, to an extent, qualitatively different and suggest there may be several mechanisms involved in the development of tolerance to and physical dependence on morphine. A part of the precipitated abstinence syndrome in the acutely physically dependent dog can be explained on the basis of a "homeostatic resensitization hypothesis. "However, spinal cord signs of precipitated abstinence in the acutely physically dependent dog cannot be explained by this hypothesis.