FUNCTIONAL CHARACTERIZATION OF ANATOMICAL SITES ASSOCIATED WITH WITHDRAWAL

药物滥用是一种慢性病，其特征是行为的长期变化。该项目旨在阐明长期接触阿片类药物导致的大脑功能持续异常。我们的研究评估了调节大鼠吗啡戒断的因素。我们实验室对大脑葡萄糖代谢的活体研究提供了证据，表明LC在阿片类药物戒断相关的神经元活动增加中发挥重要作用。将四种阿片拮抗剂甲基纳络酮直接注射到吗啡依赖大鼠的LC，而不是中央杏仁核或臂旁背侧核，可增加LC及其投射的脑葡萄糖代谢。然而，在另一位NIDA科学家(James Bell博士)的研究中，在吗啡依赖大鼠的脑片制剂中添加纳洛酮并没有增加LC的放电。这些LC介导的活性分析表明，体内LC的激活是由于通过反馈电路放大神经元的放电，而这在切片制备中是不存在的。-阿片类药物戒断、蓝斑、大鼠、药物滥用

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