Persistant cerebral metabolic effects of morphine in the presence and absence of conditioned cues, 6 and 13 days after the last morphine injection in the rat.

摘要

It has been demonstrated previously that repeated exposure of rats to morphine results in behavioral sensitization, an increased sensitivity to subsequent administrations of morphine long after the initial experience. To characterize the underlying neuroanatomical substrate of this persistent morphine effect, local cerebral metabolic rates for glucose (LCMR{dollar}sb{lcub}rm glu{rcub}{dollar}) were determined using the quantitative 2-deoxyglucose (2-DG) method. It was hypothesized that repeated experience with morphine would cause changes in basal LCM{dollar}sb{lcub}rm glu{rcub}{dollar} and that these effects would, in part, be a function of the presence of morphine cues. In order to determine the extent of these putative changes, LCMR{dollar}sb{lcub}rm glu{rcub}{dollar} was measured 6 and 13 days after the last morphine injection. The sensitization treatment consisted of 4, 10 mg/kg, sc., morphine injections during a 36 hour period. In one group, rats were placed in the experimental chamber immediately after each injection to maximize the association of the test environment with the sensitizing effects of morphine. In a parallel group, rats were placed in their home cages after each morphine injection in order to minimize the development of classical conditioning. Appropriate control groups received saline instead of the morphine regimen.; The morphine treatment significantly increased basal metabolic activity throughout the forebrain in both the presence and absence of morphine cues, although the number of significantly affected regions was greater in the group in which conditioned cues were present. These enhanced effects in the presence of the morphine cues suggest a relevance of these findings for the phenomena of "drug craving" in the opiate addict, a phenomenon that is often triggered by the presence of drug-associated cues.; Among the brain regions showing increases in the morphine treated rats at both 6 and 13 days were components of the corticostriatal-pallidothalamic-thalamocortical circuit involving the nucleus accumbens shell. This circuit has been implicated in motivation and positive reinforcement, and therefore these protracted morphine effects have implications for a greater understanding for both craving and recidivism in the nonmedical use of opiates.