中国科学院心理健康重点实验室知识库

药物成瘾会导致相关神经环路的结构和功能长期改变。大量新的研究证据表明,在DNA序列不变的情况下,药物成瘾可通过影响不同亚型DNA甲基转移酶(DNMTs)的表达,使脑内多个相关核团发生DNA甲基化以及基因表达的改变,进而导致神经元功能的可塑性变化。因此,DNA甲基化被视作导致成瘾行为长期存在的可能机制之一。结合近几年来的重要发现,本文将重点讨论相关脑区的DNA甲基化在成瘾行为发生发展过程中的作用,以及成瘾药物影响DNA甲基化水平的可能机制,并试图提出可深入的研究展望。

Drug addiction induces long-term changes in the structure and function of the addiction-related circuitries. Recent studies suggested that drug abuse induced the changes of DNA methylation and gene expression in addiction-related nuclei by modulating the expression of three types of DNA methyltransferases （DNMTs） without changing DNA sequences, which in turn changed the functional neural plasticity. Therefore, DNA methylation is regarded as one of the possible mechanisms underlying persistent addictive behavior. In this review we discuss recent advances in our understanding of how DNA methylation contribute to the addictive behavior and how abusive drugs regulate the DNA methylation, and further proposed a few important directions for future research in the field.