As an individual becomes addicted to a drug of abuse, nerve cells within the brain's reward circuitry adapt at the epigenetic level during the course of repeated drug exposure. These drug-induced epigenetic adaptations mediate enduring changes in brain function which contribute to life-long, drug-related behavioral abnormalities that define addiction. Targeting these epigenetic alterations will enhance our understanding of the biological basis of addiction and might even yield more effective anti-addiction therapies. However, the complexity of the neuroepigenetic landscape makes it difficult to determine which drug-induced epigenetic changes causally contribute to the pathogenic mechanisms of drug addiction. In this review, we highlight the evidence that epigenetic modifications, specifically histone modifications, within key brain reward regions are correlated with addiction. We then discuss the emerging field of locus-specific neuroepigenetic editing, which is a promising method for determining the causal epigenetic molecular mechanisms that drive an addicted state. Such approaches will substantially increase the field's ability to establish the precise epigenetic mechanisms underlying drug addiction, and could lead to novel treatments for addictive disorders.

中文翻译：

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表观遗传学和成瘾。

当个人沉迷于滥用药物时，在反复接触药物的过程中，大脑奖励回路内的神经细胞会在表观遗传水平上适应。这些药物诱导的表观遗传适应介导了大脑功能的持久变化，从而导致终身，与药物相关的行为异常，这些异常定义了成瘾。针对这些表观遗传学改变将增强我们对成瘾的生物学基础的理解，甚至可能产生更有效的抗成瘾疗法。然而，神经表观遗传学的复杂性使得很难确定哪些药物诱导的表观遗传学改变是造成药物成瘾的致病机制的原因。在这篇评论中，我们重点介绍了表观遗传修饰，特别是组蛋白修饰，关键的大脑奖励区域内的成瘾与成瘾有关。然后，我们讨论基因座特异性神经表观遗传编辑的新兴领域，这是一种确定驱动成瘾状态的因果表观遗传分子机制的有前途的方法。这种方法将大大提高该领域建立起药物成瘾基础的精确表观遗传机制的能力，并可能导致对成瘾性疾病的新颖治疗。