MicroRNAs Modulate Interactions between Stress and Risk for Cocaine Addiction.
MicroRNAs Modulate Interactions between Stress and Risk for Cocaine Addiction.
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DOI：
10.3389/fncel.2016.00125
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发表时间：
2016
影响因子：
5.3
通讯作者：
Unterwald EM
中科院分区：
文献类型：
--
作者：
Doura MB;Unterwald EM
暴露在压力下会增加吸毒的可能性，以及成瘾者复发的可能性。长期吸毒会改变压力反应，从而增加吸毒行为和复发。药物暴露和戒断已被证明会改变压力反应，而压力的皮质类固醇介质已被证明会影响与成瘾相关的大脑功能和寻求药物的行为。尽管压力和药物滥用之间的相互作用已有记录，但压力暴露和药物寻求相互作用的机制仍然很大程度上未知。最近的研究表明，microRNA (miRNA) 在压力调节以及成瘾相关过程中发挥着重要作用，包括神经发生、突触发育、可塑性、药物获取、戒断和复发。 MiRNA 是短非编码 RNA，通过 mRNA 的不完美序列靶向降解和/或翻译抑制，充当基因表达的双向表观遗传调节剂。它们作为中枢神经系统生理学和病理生理学的动态调节器，促进复杂系统和行为的快速和持久的变化。 miRNA 在糖皮质激素信号传导和中脑边缘多巴胺奖赏系统以及与药物戒断相关的情绪障碍中发挥作用。文献表明，miRNA 在压力暴露、成瘾相关过程以及长期停药导致的负面情感状态之间的相互作用中发挥着关键作用。本手稿回顾了 miRNA 在调节应激和可卡因反应中的作用的最新证据，并讨论了 miRNA 对这些系统相互作用的潜在介导。揭示压力与吸毒之间关联背后的机制有可能影响药物滥用的治疗和预防复发。对这些复杂相互作用的进一步理解可能为药物成瘾的治疗提供有希望的新靶点。
Exposure to stress increases vulnerability to drug abuse, as well as relapse liability in addicted individuals. Chronic drug use alters stress response in a manner that increases drug seeking behaviors and relapse. Drug exposure and withdrawal have been shown to alter stress responses, and corticosteroid mediators of stress have been shown to impact addiction-related brain function and drug-seeking behavior. Despite the documented interplay between stress and substance abuse, the mechanisms by which stress exposure and drug seeking interact remain largely unknown. Recent studies indicate that microRNAs (miRNA) play a significant role in stress modulation as well as addiction-related processes including neurogenesis, synapse development, plasticity, drug acquisition, withdrawal and relapse. MiRNAs are short non-coding RNAs that function as bidirectional epigenetic modulators of gene expression through imperfect sequence targeted degradation and/or translational repression of mRNAs. They serve as dynamic regulators of CNS physiology and pathophysiology, and facilitate rapid and long-lasting changes to complex systems and behaviors. MiRNAs function in glucocorticoid signaling and the mesolimbic dopamine reward system, as well as mood disorders related to drug withdrawal. The literature suggests miRNAs play a pivotal role in the interaction between exposures to stress, addiction-related processes, and negative affective states resulting from extended drug withdrawal. This manuscript reviews recent evidence for the role of miRNAs in the modulation of stress and cocaine responses, and discusses potential mediation of the interaction of these systems by miRNAs. Uncovering the mechanism behind the association of stress and drug taking has the potential to impact the treatment of drug abuse and prevention of relapse. Further comprehension of these complex interactions may provide promising new targets for the treatment of drug addiction.