Maldonado R
Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM-URA D 1500 CNRS, UFR des Sciences Pharmaceutiques et Biologiques, Université René Descartes-Faculté de Pharmacie, Paris, France.
Neurosci Biobehav Rev. 1997 Jan;21(1):91-104. doi: 10.1016/0149-7634(95)00061-5.
Several lines of biochemical and pharmacological evidence provide support for the involvement of the noradrenergic system in the expression of the somatic symptoms of opiate withdrawal. Early studies reported changes in brain noradrenaline and metabolite levels during opiate dependence. The significance of these changes has been clarified in recent microdialysis studies indicating that acute morphine decreases the extraneuronal levels of noradrenaline, whereas an increase in release of the neurotransmitter occurs during opiate withdrawal in several brain areas. Changes in the sensitivity and density of alpha 2- and beta-adrenoceptors have also been reported, probably as a consequence of the decreased presynaptic noradrenergic activity induced during morphine dependence. In addition, the administration of alpha 2-agonists, such as clonidine, or beta-antagonists, such as propranolol, has been reported to attenuate some manifestations of opiate withdrawal. The noradrenergic structure mediating the expression of opioid abstinence seems to be the locus coeruleus. However, the activation of the locus coeruleus during morphine withdrawal seems to be primarily due to the afferent projections containing excitatory amino acids and derived from the nucleus paragigantocellularis, although intrinsic modifications, consisting of an up-regulation of the cAMP pathway, seem also to be involved in this activation. The participation of the mesolimbic dopaminergic system in opiate dependence and its relation with the changes produced in the noradrenergic system are also discussed.
多条生化和药理学证据支持去甲肾上腺素能系统参与阿片类药物戒断躯体症状的表达。早期研究报道了阿片类药物依赖期间脑内去甲肾上腺素和代谢物水平的变化。近期的微透析研究阐明了这些变化的意义，表明急性给予吗啡可降低去甲肾上腺素的神经元外水平，而在阿片类药物戒断期间，几个脑区的神经递质释放会增加。也有报道称α2和β肾上腺素能受体的敏感性和密度发生了变化，这可能是吗啡依赖期间诱导的突触前去甲肾上腺素能活性降低的结果。此外，据报道，给予α2激动剂（如可乐定）或β拮抗剂（如普萘洛尔）可减轻阿片类药物戒断的一些表现。介导阿片类药物戒断症状表达的去甲肾上腺素能结构似乎是蓝斑。然而，吗啡戒断期间蓝斑的激活似乎主要是由于含有兴奋性氨基酸且来自巨细胞旁核的传入投射，尽管由cAMP途径上调组成的内在修饰似乎也参与了这种激活。本文还讨论了中脑边缘多巴胺能系统在阿片类药物依赖中的参与及其与去甲肾上腺素能系统产生的变化的关系。
