PERSISTENT INCREASES IN BASAL CEREBRAL METABOLIC-ACTIVITY INDUCED BY MORPHINE SENSITIZATION

To characterize the underlying neuroanatomic substrate of morphine (MS ) sensitization, changes in the local cerebral metabolic rate for gluc ose (LCMRglu) were examined in 95 brain regions of male F-344 rats usi ng the 2-deoxy-D-[1-C-14]glucose method. The results of these experime nts demonstrate that MS-induced sensitization is manifested by increas es in basal metabolic activity that last for at least 6 days. Although changes in basal metabolic rate were found to be more extensive in th e presence of conditioned cues, the increases in LCMRglu in nonconditi oned sensitized rats indicate a basic underlying pharmacologic effect of MS sensitization on basal brain activity. Regions in which MS sensi tization had a lasting pharmacologic effect include the shell of the n ucleus accumbens, the prelimbic area of the prefrontal cortex, and the dorsolateral prefrontal cortex. Interestingly, the core of the nucleu s accumbens and regions of the caudate were found to have an increased LCMRglu only in the presence of conditioned cues, indicating conditio ned brain activity without observable changes in behavior. The previou s administration of an MS-sensitizing treatment was also found to afte r the cerebral metabolic response to a subsequent acute MS challenge ( 0.5 mg/kg, subcutaneously), most notably in forebrain systems. The mor e widespread activation of brain structures in the basal state in the presence of conditioned cues suggests that these MS-sensitized rats ma y model an altered brain state related to craving in the abstinent opi ate addict. (C) 1997 Elsevier Science Inc.