Koob George F, Simon Eric J
J Drug Issues. 2009 Jan;39(1):115-132. doi: 10.1177/002204260903900110.
A number of dramatic breakthroughs in the neurobiology of addiction have occurred in the past 40 years. Two domains will be highlighted: the neurocircuitry of addiction and the molecular biology of addiction targets. The neurobiological substrates for the reinforcing effects of drugs of abuse have been largely identified both at the initial site of action and in the circuitry involved. In human imaging studies, decreases in dopaminergic function have been identified as a key element of addiction, lending support for research on the role of dopamine in addiction. Three novel areas currently are emerging: the role of deficits in frontal cortex functioning, changes in the brain neurocircuitry that convey long-term vulnerability to relapse, and the role of nondopaminergic systems in the neuroadaptations associated with the development of drug dependence. Parallel to these functional changes have been major advances in our understanding of the molecular biology of addiction; the greatest contribution has been in the understanding of the molecular mechanisms of opioid action. This paper reviews the major developments in our understanding of the molecular biology of the endogenous opioid system and the use of genomics to advance our knowledge of the function and regulation of opioid receptors and endorphins.
在过去40年里，成瘾神经生物学领域取得了一些重大突破。将重点介绍两个领域：成瘾的神经回路和成瘾靶点的分子生物学。滥用药物强化作用的神经生物学底物在其初始作用部位和相关神经回路中已基本明确。在人体成像研究中，多巴胺能功能下降已被确定为成瘾的关键因素，这为研究多巴胺在成瘾中的作用提供了支持。目前正在出现三个新领域：额叶皮质功能缺陷的作用、传达长期复发易感性的脑内神经回路变化以及非多巴胺能系统在与药物依赖发展相关的神经适应性中的作用。与这些功能变化并行的是，我们对成瘾分子生物学的理解取得了重大进展；最大的贡献在于对阿片类药物作用分子机制的理解。本文综述了我们对内源性阿片系统分子生物学的主要认识进展，以及利用基因组学增进我们对阿片受体和内啡肽功能及调节的认识。
