MicroRNA-31-3p/RhoA signaling in the dorsal hippocampus modulates methamphetamine-induced conditioned place preference in mice

MicroRNA-31-3p/RhoA signaling in the dorsal hippocampus modulates methamphetamine-induced conditioned place preference in mice
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背侧海马中的 MicroRNA-31-3p/RhoA 信号调节甲基苯丙胺诱导的小鼠条件性位置偏好

DOI:
10.1007/s00213-021-05936-2
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发表时间:
2021-07
期刊:
Psychopharmacology (Berl)
影响因子:
--
通讯作者:
Xinshe Liu
Xinshe Liu
中科院分区:
其他
文献类型:
--
作者:
Hongyan Qian;Qing Shang;Min Liang;Baoyao Gao;Jing Xiao;Jing Wang;Axiang Li;Canyu Yang;Jianmin Yin;Gang Chen;Tao Li;Xinshe Liu

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微小RNA(miRNAs)调节与神经可塑性相关的蛋白质,并与甲基苯丙胺(METH)成瘾有关。RhoA是一种小的Rho GTP酶,可调节突触可塑性和成瘾行为。然而,R……之间的功能关系(句子不完整)
RationaleMicroRNAs (miRNAs) regulate neuroplasticity-related proteins and are implicated in methamphetamine (METH) addiction. RhoA is a small Rho GTPase that regulates synaptic plasticity and addictive behaviors. Nevertheless, the functional relationship between RhoA and upstream miRNAs of METH addiction remains unclear.ObjectiveTo explore the molecular biology and epigenetic mechanisms of the miR-31-3p/RhoA pathway in METH addiction.MethodsRhoA protein and its potential upstream regulator, miR-31-3p, were detected. A dual luciferase reporter was employed to determine whether RhoA constituted a specific target of miR-31-3p. Following adeno-associated virus (AAV)-mediated knockdown or overexpression of miR-31-3p or RhoA in the dorsal hippocampus (dHIP), mice were subjected to conditioned place preference (CPP) to investigate the effects of miR-31-3p and RhoA on METH-induced addictive behaviors.ResultsRhoA protein was significantly decreased in the dHIP of CPP mice with a concomitant increase in miR-31-3p. RhoA was identified as a direct target of miR-31-3p. Knockdown of miR-31-3p in the dHIP was associated with increased RhoA protein and attenuation of METH-induced CPP. Conversely, overexpression of miR-31-3p was associated with decreased RhoA protein and enhancement of METH effects. Similarly, knockdown of RhoA in the dHIP enhanced METH-induced CPP, whereas RhoA overexpression attenuated the effects of METH. Parallel experiments using sucrose preference revealed that the effects of miR-31-3p/RhoA pathway modulation were specific to METH.ConclusionsOur findings indicate that the miR-31-3p/RhoA pathway in the dHIP modulates METH-induced CPP in mice. Our results highlight the potential role of epigenetics represented by non-coding RNAs in the treatment of METH addiction.
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