药物成瘾的表观遗传学机制研究进展

Progress in research of epigenetic mechanisms of drug addiction

药物成瘾是一种慢性、复发性脑疾病,其特点主要表现为以不计后果的强迫性用药和对药物的持续渴求。药物滥用会导致神经结构和功能可塑性的改变,造成分子、细胞和整体水平的适应性改变,从而引起个体终身行为异常。目前研究发现,表观遗传学改变导致的持续性基因表达改变是药物成瘾的重要机制。研究表明,重复暴露于滥用性药物在大脑的奖赏区域会发生表观遗传学改变,主要有以下3种调控方式:组蛋白修饰(例如乙酰化和甲基化)、DNA甲基化和非编码RNA调控。药物成瘾的表观遗传学的研究将为药物成瘾的遗传学和非遗传学的分子调控机制的理解提供新视角,并为临床药物成瘾的表观遗传学治疗研究提供新方向和新思路。本文将对近年来药物成瘾的表观遗传学研究进展作系统的综述。

Drug addiction is a chronic relapsing brain disease that is characterized by compulsive drug use and persistence of drug craving. Drug abuse can lead to changes in the neuron structure and function of plasticity,alterations in molecules and cells,and ultimately to individual abnormal behavior.Current studies have found that epigenetic changes leading to the sustainability of gene expression is an important mechanism of drug addiction. In this review,we will systematically summarize the latest advances in epigenetic mechanisms of drug addiction. This review is expected to provide robust evidence that repeated exposure to drugs of abuse induces changes within the brain′s reward regions in three major modes of epigenetic regulation- histone modifications such as acetylation and methylation,DNA methylation,and non-coding RNAs. It promises a new perspective from which to gain insights into the genetic and epigenetic mechanisms of drug addiction and a new area for epigenetic research on clinical drug addiction treatment.