Persistent Increases in Basal Cerebral Metabolic Activity Induced by Morphine Sensitization

Abstract

To characterize the underlying neuroanatomic substrate of morphine (MS) sensitization, changes in the local cerebral metabolic rate for glucose (LCMR glu) were examined in 95 brain regions of male F-344 rats using the 2-deoxy-D-[1- 14C]glucose method. The results of these experiments demonstrate that MS-induced sensitization is manifested by increases in basal metabolic activity that last for at least 6 days. Although changes in basal metabolic rate were found to be more extensive in the presence of conditioned cues, the increases in LCMR glu in nonconditioned sensitized rats indicate a basic underlying pharmacologic effect of MS sensitization on basal brain activity. Regions in which MS sensitization had a lasting pharmacologic effect include the shell of the nucleus accumbens, the prelimbic area of the prefrontal cortex, and the dorsolateral prefrontal cortex. Interestingly, the core of the nucleus accumbens and regions of the caudate were found to have an increased LCMR glu only in the presence of conditioned cues, indicating conditioned brain activity without observable changes in behavior. The previous administration of an MS-sensitizing treatment was also found to alter the cerebral metabolic response to a subsequent acute MS challenge (0.5 mg/kg, subcutaneously), most notably in forebrain systems. The more widespread activation of brain structures in the basal state in the presence of conditioned cues suggests that these MS-sensitized rats may model an altered brain state related to craving in the abstinent opiate addict.