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滥用药物:毒性和成瘾中的表观遗传机制。

Drugs of abuse: epigenetic mechanisms in toxicity and addiction.

机构信息

Laboratory of Forensic Medicine & Toxicology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

出版信息

Curr Med Chem. 2011;18(12):1765-74. doi: 10.2174/092986711795496836.

Abstract

The abuse of substances such as ethanol, cocaine, amphetamines and heroin is associated with toxic effects on almost every system of the organism. Furthermore, the transition from occasional-recreational use to chronic abuse and addiction is a serious psychiatric disorder with only few chances for effective and definitive treatment since most individuals relapse, even after long periods of abstinence. It is therefore of utmost importance to elucidate the mechanisms by which these substances exert their toxicity and mediate addiction, in order to develop new, efficient therapeutic strategies with a long-term outcome, which are currently lacking. We already know that in a great number of these mechanisms, altered gene function is involved. But, with the new field of epigenetics, there is increasing evidence that changes in the epigenome are responsible for the altered gene function. The advances in the field of epigenetics towards elucidation of the mechanisms underlying toxicity and addiction for ethanol, cocaine, amphetamines and heroin are currently presented and discussed in this review.

摘要

滥用乙醇、可卡因、安非他命和海洛因等物质会对人体几乎每个系统造成毒性影响。此外,从偶尔的娱乐性使用过渡到慢性滥用和成瘾是一种严重的精神障碍,只有极少数有效的、明确的治疗机会,因为大多数个体即使在长时间戒断后也会复发。因此,阐明这些物质发挥毒性和介导成瘾的机制至关重要,以便开发新的、有效的治疗策略,目前缺乏长期效果的治疗策略。我们已经知道,在大量的这些机制中,涉及基因功能的改变。但是,随着表观遗传学领域的发展,越来越多的证据表明,表观基因组的改变导致了基因功能的改变。本文目前就乙醇、可卡因、安非他命和海洛因的毒性和成瘾机制的表观遗传学研究进展进行了综述和讨论。

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