Table1_Striatal miR-183-5p inhibits methamphetamine-induced locomotion by regulating glucocorticoid receptor signaling.XLSX

MicroRNA (miRNA)-mediated striatal gene regulation may play an important role in methamphetamine (METH) addiction. This study aimed to identify changes in novel miRNAs and their target genes during METH self-administration and investigate their roles in METH-induced locomotion. RNA sequencing analysis revealed that mir-183-5p was upregulated in the striatum of METH self-administered rats, and target gene prediction revealed that the glucocorticoid receptor (GR) gene, Nr3c1, was a potential target gene for mir-183-5p. We confirmed that single and repeated METH administrations increased METH-induced locomotion and plasma corticosterone levels in rats. Additionally, increased miR-185-5p expression and decreased GR gene expression were observed only in the repeated-METH-injection group but not in the single-injection group. We then investigated the effects of miR-183-5p on METH-induced locomotion using a miR-183-5p mimic and inhibitor. Injection of a mir-183-5p mimic in the striatum of rats attenuated METH-induced locomotion, whereas injection of a miR-183-5p inhibitor enhanced the locomotor activity in METH-administered rats. Furthermore, the miR-183-5p mimic reduced the phosphorylation of tyrosine hydroxylase (TH) whereas the inhibitor increased it. Taken together, these results indicate that repeated METH injections increase striatal miR-183-5p expression and regulate METH-induced locomotion by regulating GR expression in rats, thereby suggesting a potential role of miR-183-5p as a novel regulator of METH-induced locomotion.

微小RNA（miRNA）介导的纹状体基因调控可能在甲基苯丙胺（METH）成瘾中发挥重要作用。本研究旨在鉴定甲基苯丙胺自身给药过程中新型miRNA及其靶基因的表达变化，并探究其在甲基苯丙胺诱导的运动活动中的作用。RNA测序分析显示，甲基苯丙胺自身给药大鼠的纹状体中mir-183-5p表达上调；靶基因预测结果表明，糖皮质激素受体（GR）基因Nr3c1是mir-183-5p的潜在靶基因。我们证实，单次和重复给予甲基苯丙胺均可增强大鼠的甲基苯丙胺诱导运动活性，并升高血浆皮质酮水平。此外，仅在重复甲基苯丙胺注射组中观察到miR-185-5p表达升高与GR基因表达降低，单次注射组未出现该变化。我们进一步利用miR-183-5p模拟物与抑制剂，探究其对甲基苯丙胺诱导运动活性的影响。向大鼠纹状体注射mir-183-5p模拟物可减弱甲基苯丙胺诱导的运动活性，而注射miR-183-5p抑制剂则可增强甲基苯丙胺给药大鼠的运动能力。此外，mir-183-5p模拟物可降低酪氨酸羟化酶（TH）的磷酸化水平，而抑制剂则可升高该磷酸化水平。综上，本研究结果表明，重复给予甲基苯丙胺可升高大鼠纹状体中miR-183-5p的表达，并通过调控GR基因表达来调节甲基苯丙胺诱导的运动活性，提示miR-183-5p或可作为甲基苯丙胺诱导运动活性的新型调控因子。