Rasmussen K
Central Nervous System Research, Eli Lilly and Co., Indianapolis, IN.
Prog Brain Res. 1991;88:207-16. doi: 10.1016/s0079-6123(08)63810-8.
The locus coeruleus (LC) has been hypothesized to play an important role in opiate withdrawal. This hypothesis is supported, in part, by the finding that LC neurons greatly increase their activity during antagonist-precipitated morphine withdrawal and that this increased activity correlates temporally with withdrawal behavior. However, this withdrawal-induced increase in unit activity is not seen in vitro in brain slices taken from morphine-dependent animals, indicating that afferents to the LC play an important role in the withdrawal-induced activation of these neurons. This chapter reviews data indicating: (1) the morphine-withdrawal-induced activation of LC neurons is mediated predominantly by non-N-methyl-D-aspartate (NMDA) excitatory amino acid pathways in the brain; (2) the activation of the LC during morphine withdrawal may be mediated, at least in part, by an excitatory amino acid projection from the nucleus paragigantocellularis. The role of other excitatory amino acid pathways in the withdrawal-induced activation of the LC remains to be determined; (3) intrinsic changes in the G-protein/cyclic AMP system of LC cells may play an important role in mediating the effects of afferent inputs to the LC during morphine withdrawal; (4) NMDA antagonists (unlike the alpha 2 agonist clonidine) attenuate the behavioral signs of morphine withdrawal without blocking the withdrawal-induced increase of LC unit activity. In addition, non-competitive NMDA antagonists like MK801 may not be useful to alleviate opiate-withdrawal symptoms in man because of their PCP-like side effects. However, competitive NMDA antagonists like LY274614 could be of great benefit for alleviating opiate-withdrawal withdrawal symptoms in man.
蓝斑（LC）被认为在阿片类药物戒断中起重要作用。这一假说部分得到了以下发现的支持：在拮抗剂诱发的吗啡戒断期间，LC神经元的活动大幅增加，且这种增加的活动在时间上与戒断行为相关。然而，在从吗啡依赖动物获取的脑片中，体外实验未观察到这种戒断诱导的单位活动增加，这表明向LC的传入神经在这些神经元的戒断诱导激活中起重要作用。本章综述了相关数据，表明：（1）吗啡戒断诱导的LC神经元激活主要由脑中的非N - 甲基 - D - 天冬氨酸（NMDA）兴奋性氨基酸通路介导；（2）吗啡戒断期间LC的激活可能至少部分由来自巨细胞旁核的兴奋性氨基酸投射介导。其他兴奋性氨基酸通路在戒断诱导的LC激活中的作用仍有待确定；（3）LC细胞的G蛋白/环磷酸腺苷系统的内在变化可能在介导吗啡戒断期间传入LC的输入效应中起重要作用；（4）NMDA拮抗剂（与α2激动剂可乐定不同）可减轻吗啡戒断的行为体征，但不阻断戒断诱导的LC单位活动增加。此外，像MK801这样的非竞争性NMDA拮抗剂可能因具有类似苯环己哌啶的副作用而对缓解人类阿片类药物戒断症状无用。然而，像LY274614这样的竞争性NMDA拮抗剂可能对缓解人类阿片类药物戒断症状有很大益处。
