Cerebral glucose metabolism during opioid withdrawal following methylnaloxonium injection into the locus coeruleus

Abstract

Previous studies have demonstrated a widespread stimulation of regional cerebral metabolic rate(s) for glucose (rCMRglc) in morphine-dependent rats subjected to opioid withdrawal precipitated by systemic injection of naloxone. Nonetheless, many of the behavioral signs of opioid withdrawal are produced by intracerebral injections of an opioid antagonist, methylnaloxonium (MN), into the locus coeruleus (LC). The purpose of the present work was to determine the extent to which cerebral metabolic alterations in opioid withdrawal could be initiated by a local action in LC. Intracerebral injections of MN into LC increased rCMRglc in morphine-dependent rats, and the anatomical distribution of this effect was similar to that produced by systemic injections of naloxone. The present data support the view that LC is a major substrate of opioid withdrawal in the brain, and they suggest that LC plays an important role in changing rCMRglc during opioid withdrawal induced by systemic naloxone administration.