CONTEXT MicroRNA (miRNA) is an important regulator of gene expression. Methamphetamine (METH) induces a variety of alterations in different systems by affecting gene expression, but the effects of METH on miRNA profiles need to be elucidated. OBJECTIVES This study develops a rat model of METH addiction, and analyzes the expression profile alterations of miRNA in nucleus accumbens (NAc) of the METH-addicted rats. MATERIALS AND METHODS Sprague-Dawley rats were administered 10 mg/kg METH or vehicle twice a day for 4 weeks. The addictive behaviour of rats was estimated by CPP test. The pathological changes of brain tissues were then observed by HE and Glee silver staining. The miRNA profile analysis of the NAc of the rats was performed using an Illumina HiSeq™ 2500 sequencing system. RESULTS CPP test indicated that METH significantly prolonged the residence time of the rats in the drug box (from 307 ± 97 to 592 ± 96 s). The pathological staining showed the distorted axons, and fewer polarized neurons in the METH-treated rats. We further identified 40 differential miRNAs (17 up- and 23 down-regulated) and three novel miRNAs (novel 237, 296 and 501) that responded to METH. The bioinformatic analysis for the potential targets of the differential miRNA suggests that the downstream were concentrated in the Wnt signalling pathway, tuberculosis, toxoplasmosis, spliceosome, lysosome, and axon guidance. DISCUSSION AND CONCLUSIONS A number of miRNAs responding to METH were identified in the NAc of rats. These METH-regulated miRNAs provide a new perspective for revealing the molecular mechanisms of METH addiction.

中文翻译：

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甲基苯丙胺导致大鼠伏核中 microRNA 谱的改变

上下文 MicroRNA (miRNA) 是基因表达的重要调节因子。甲基苯丙胺 (METH) 通过影响基因表达诱导不同系统的各种改变，但需要阐明 METH 对 miRNA 图谱的影响。目的 本研究建立了 METH 成瘾大鼠模型，并分析了 METH 成瘾大鼠伏隔核 (NAc) 中 miRNA 表达谱的变化。材料和方法 Sprague-Dawley 大鼠每天两次服用 10 mg/kg METH 或载体，持续 4 周。通过CPP测试评估大鼠的成瘾行为。HE和Glee银染观察脑组织病理变化。使用 Illumina HiSeq™ 2500 测序系统对大鼠的 NAc 进行 miRNA 图谱分析。结果 CPP试验表明METH显着延长了大鼠在药箱中的停留时间（从307±97到592±96 s）。病理染色显示，METH 处理的大鼠轴突扭曲，极化神经元减少。我们进一步鉴定了 40 种差异 miRNA（17 种上调和 23 种下调）和三种对 METH 有反应的新型 miRNA（新型 237、296 和 501）。差异miRNA潜在靶点的生物信息学分析表明，下游主要集中在Wnt信号通路、结核病、弓形虫病、剪接体、溶酶体和轴突导向。讨论和结论 在大鼠的 NAc 中鉴定出许多对 METH 有反应的 miRNA。这些 METH 调节的 miRNA 为揭示 METH 成瘾的分子机制提供了新的视角。