Drug abuse is a chronic disease, characterized by long-term changes in behavior. This project is geared at elucidating persistent abnormalities in brain function induced by long-term exposure to opiates. Our study evaluated factors that modulate morphine withdrawal in the rat. In vivo studies of brain glucose metabolism from our laboratory have provided evidence that the LC plays an important role in the increased neuronal activity associated with opiate withdrawal. The microinjection of methylnaloxonium, a quaternary opioid antagonist, directly into the LC but not in the central amygdala or dorsal parabrachial nucleus of morphine-dependent rats increases cerebral glucose metabolism in the LC and its projections. Nonetheless in studies by another NIDA scientist (Dr. James Bell), addition of naloxone to a brain slice preparation from morphine-dependent rats did not increase LC firing. These assays of LC-mediated activity suggest that LC activation in vivo is due to an amplification of neuronal firing via feedback circuits, which are absent in the slice preparation. - opioid withdrawal, locus coeruleus, rats, drug abuse
