FUNCTIONAL CHARACTERIZATION OF ANATOMICAL SITES ASSOCIATED WITH WITHDRAWAL

因为吸毒是一种慢性病， 以行为的长期变化为特征，这个项目是 致力于阐明大脑功能的持续性异常 由药物滥用引起的，包括鸦片类药物和兴奋剂。我们的 研究评估了调节吗啡戒断的因素 老鼠。在阿片类药物戒断过程中，轨迹的加速放电 蓝斑(LC)神经元提示了LC的功能作用。 在吗啡依赖大鼠的脑片中，LC的放电频率是 由于不完全公差而被抑制。纳洛酮退回LC 射击率控制，但不是超常的射击率 需要激活切片中不存在的外在通路。这 观察挑战了普遍接受的概念，即LC细胞， 在戒断时，启动兴奋性活动。然而， 我们实验室的其他活体研究提供了证据 LC启动与以下相关的神经元活动增加 鸦片类药物戒断。甲基纳洛酮微量注射 第四代阿片类拮抗剂，直接进入LC但不进入LC 杏仁中央核或臂旁背侧核 吗啡依赖大鼠脑内葡萄糖代谢增加 LC及其预测。体外培养的细胞之间的差异 体内LC活性分析表明，LC在体内激活 是由于反馈电路放大了神经元的放电， 这在切片制备中是不存在的。

Because 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 drugs of abuse, including opiates and stimulants. Our studies evaluated factors that modulate morphine withdrawal in the rat. During opiate withdrawal, the accelerated firing of locus coeruleus (LC) neurons has suggested a functional role of the LC. In slices from morphine dependent rats, LC firing rates were suppressed due to incomplete tolerance. Naloxone returned LC firing rates to control, but not supernormal rates demonstrating a need for activation of extrinsic pathways absent in the slice. This observation challenges the generally accepted concept that LC cells, themselves, initiate excitatory activity in withdrawal. However, other in vivo studies from our laboratory have provided evidence that the LC initiates increases in 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. The discrepancy between the in vitro and in vivo assays of LC activity suggests that LC activation in vivo is due to an amplification of neuronal firing via feedback circuits, which are absent in the slice preparation.