Deehan Gerald A, Brodie Mark S, Rodd Zachary A
Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA.
Curr Top Behav Neurosci. 2013;13:163-84. doi: 10.1007/7854_2011_198.
Alcohol abuse and alcoholism represent substantial problems that affect a large portion of individuals throughout the world. Extensive research continues to be conducted in an effort to identify the biological basis of the reinforcing properties of alcohol in order to develop effective pharmacotherapeutic and behavioral interventions. One theory that has developed within the alcohol field over the past four decades postulates that the reinforcing properties of alcohol are due to the action of the metabolites/products of alcohol within the central nervous system (CNS). The most extreme version of this theory suggests that the biologically active metabolites/products of alcohol, created from the breakdown from alcohol, are the ultimate source of the reinforcing properties of alcohol. The contrary theory proposes that the reinforcing properties of alcohol are mediated completely through the interaction of the ethanol molecule with several neurochemical systems within the CNS. While there are scientific findings that offer support for both of these stances, the reinforcing properties of alcohol are most likely generated through a complex series of peripheral and central effects of both alcohol and its metabolites. Nonetheless, the development of a greater understanding for how the metabolites/products of alcohol contribute to the reinforcing properties of alcohol is an important factor in the development of efficacious pharmacotherapies for alcohol abuse and alcoholism. This chapter is intended to provide a historical perspective of the role of acetaldehyde (the first metabolite of alcohol) in alcohol reinforcement as well as review the basic research literature on the effects of acetaldehyde (and acetaldehyde metabolites/products) within the CNS and how these function with regard to alcohol reward.
酒精滥用和酒精中毒是影响全球很大一部分人的重大问题。为了确定酒精强化作用的生物学基础,以便开发有效的药物治疗和行为干预措施,人们持续进行着广泛的研究。在过去的四十年里,酒精领域发展出了一种理论,该理论假定酒精的强化作用归因于酒精在中枢神经系统(CNS)内的代谢产物的作用。这种理论最极端的版本认为,酒精分解产生的具有生物活性的代谢产物是酒精强化作用的最终来源。相反的理论则提出,酒精的强化作用完全是通过乙醇分子与中枢神经系统内的几个神经化学系统的相互作用来介导的。虽然有科学发现支持这两种观点,但酒精的强化作用很可能是通过酒精及其代谢产物一系列复杂的外周和中枢效应产生的。尽管如此,更深入地了解酒精代谢产物如何对酒精的强化作用产生影响,是开发针对酒精滥用和酒精中毒的有效药物疗法的一个重要因素。本章旨在提供乙醛(酒精的第一种代谢产物)在酒精强化作用中作用的历史视角,并回顾关于乙醛(及其代谢产物)在中枢神经系统内的作用以及这些作用与酒精奖赏功能关系的基础研究文献。
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