FUNCTIONAL CHARACTERIZATION OF ANATOMICAL SITES ASSOCIATED WITH WITHDRAWAL

药物滥用是一种慢性疾病，其特点是行为的长期改变。该项目旨在阐明长期接触阿片类药物引起的脑功能持续异常。我们的研究评估了调节大鼠吗啡戒断的因素。我们实验室对脑葡萄糖代谢的体内研究提供了证据，证明LC在阿片戒断相关的神经元活动增加中起重要作用。甲基纳洛溴铵是一种第四纪阿片拮抗剂，直接注射到吗啡依赖大鼠的LC，而不是在杏仁核中央或臂旁核背侧注射，增加了LC及其投影区的脑葡萄糖代谢。尽管如此，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切片制备中加入纳洛酮并没有增加LC放电。这些LC介导的活性分析表明，体内LC激活是由于通过反馈电路放大神经元放电，而这在切片制备中是不存在的。-阿片类药物戒断，蓝斑，老鼠，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