Epigenetics and psychostimulant addiction.
Epigenetics and psychostimulant addiction.
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DOI：
10.1101/cshperspect.a012047
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发表时间：
2013-03
影响因子：
5.4
通讯作者：
H. Schmidt;J. McGinty;A. West;G. Sadri-Vakili
中科院分区：
文献类型：
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作者：
H. Schmidt;J. McGinty;A. West;G. Sadri-Vakili
长期接触药物会改变大脑中的基因表达，并在神经网络中产生长期变化，这些变化是强迫性吸毒和寻求药物的基础。药物诱导的突触可塑性变化和随后的基因表达如何转化为持续的神经适应尚不清楚。新出现的证据表明，大脑中复杂的药物诱导的神经适应是由高度同步和动态的基因调控模式介导的。最近，表观遗传机制通过调节基因网络的表达来促进药物诱导的结构、突触和行为可塑性已经变得很清楚。在这里，我们回顾了组蛋白修饰、DNA甲基化和microrna的改变如何调节基因表达，并促进精神兴奋剂成瘾，重点关注慢性可卡因暴露后调节脑源性神经营养因子（BDNF）表达的表观遗传机制。识别定义精神兴奋剂成瘾的表观遗传特征可能会导致对药物渴望和复发的新颖，有效的治疗。
Chronic drug exposure alters gene expression in the brain and produces long-term changes in neural networks that underlie compulsive drug taking and seeking. Exactly how drug-induced changes in synaptic plasticity and subsequent gene expression are translated into persistent neuroadaptations remains unclear. Emerging evidence suggests that complex drug-induced neuroadaptations in the brain are mediated by highly synchronized and dynamic patterns of gene regulation. Recently, it has become clear that epigenetic mechanisms contribute to drug-induced structural, synaptic, and behavioral plasticity by regulating expression of gene networks. Here we review how alterations in histone modifications, DNA methylation, and microRNAs regulate gene expression and contribute to psychostimulant addiction with a focus on the epigenetic mechanisms that regulate brain-derived neurotrophic factor (BDNF) expression following chronic cocaine exposure. Identifying epigenetic signatures that define psychostimulant addiction may lead to novel, efficacious treatments for drug craving and relapse.