REGIONAL CEREBRAL GLUCOSE-UTILIZATION IN WITHDRAWAL FOLLOWING SYSTEMIC AND INTRACEREBROVENTRICULAR SUFENTANIL ADMINISTRATION

Regional cerebral glucose utilization (RCGU) and behavior were studied during naloxone-precipitated withdrawal in rats after chronic intravenous (IV) or intracerebroventricular (ICV) administration of sufentanil citrate, a potent, highly selective mu opiate agonist. Changes in RCGU were indistinguishable between the two groups (p<0.05) in 21 of 24 anatomically related limbic and brainstem structures known to be activated during withdrawal. Rats made dependent by ICV infusions of sufentanil had smaller RCGU changes in the lateral septal areas, lateral habenular nuclei and paratenial nuclei than rats made dependent by IV infusions of sufentanil. These observations are consistent with infusion artifact, given the proximity of these structures to the site of IVC infusion. All 24 structures had increased RCGU in experimental groups compared with controls (p<0.05). Although linear regression analysis suggests slightly greater RCGU changes in rats after IV sufentanil than in rats after ICV sufentanil (m=0.81), the changes in corresponding structures are highly correlated (r=0.96) indicating qualitatively almost identical RCGU changes. Behavioral changes paralleled RCGU changes and revealed slightly greater withdrawal in rats after IV sufentanil but no clear qualitative differences. Taken together, these results suggest that cerebral metabolic changes in withdrawal following chronic sufentanil administration result exclusively from effects at CNS opiate receptors and not from peripheral receptors. Additionally, the current study provides a model for the production of opiate dependence, by the ICV administration of a specific mu opiate receptor agonist that is relatively free of infusion artifact.