School of Pharmacy, Pharmacology Unit, University of Camerino, 62032, Camerino, Italy.
Curr Opin Neurobiol. 2013 Aug;23(4):684-91. doi: 10.1016/j.conb.2013.04.009. Epub 2013 May 3.
Research on alcohol and drug dependence has shown that the development of addiction depends on a complex interplay of psychological factors, genetic or epigenetic predisposing factors, and neurobiological adaptations induced by drug consumption. A greater understanding of the mechanisms leading to alcohol abuse will allow researchers to identify genetic variation that corresponds to a specific biological vulnerability to addiction, thus defining robust endophenotypes that might help deconstruct these complex syndromes into more tractable components. To this end, it is critical to develop a translational framework that links alterations at the molecular level, to changes in neuronal function, and ultimately to changes at the behavioral and clinical levels. Translational phenotypes can be identified by the combination of animal and human studies designed to elucidate the neurofunctional, anatomical and pharmacological mechanisms underlying the etiology of alcohol addiction. The present article offers an overview of medication development in alcoholism with a focus on the critical aspect of translational research. Moreover, significant examples of promising targets from neuropeptidergic systems, namely nociceptin/orphanin FQ and neuropeptide S are given.
酒精和药物依赖的研究表明，成瘾的发展取决于心理因素、遗传或表观遗传易感性因素以及药物消费引起的神经生物学适应的复杂相互作用。对导致酒精滥用的机制有更深入的了解，将使研究人员能够识别与特定的成瘾生物易感性相对应的遗传变异，从而定义强大的内表型，这些内表型可能有助于将这些复杂的综合征分解为更易于处理的成分。为此，必须制定一个转化框架，将分子水平的改变与神经元功能的改变联系起来，最终与行为和临床水平的改变联系起来。通过设计旨在阐明酒精成瘾病因的神经功能、解剖和药理学机制的动物和人类研究，可以确定转化表型。本文概述了酒精中毒药物治疗的发展，重点介绍转化研究的关键方面。此外，还给出了神经肽系统中有希望的靶标（即孤啡肽/孤啡肽 FQ 和神经肽 S）的重要示例。
