2. Academic Validation
  3. A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects

A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects

  • Mol Psychiatry. 2022 Jun 17. doi: 10.1038/s41380-022-01651-2.
Li Zhu 1 2,  Feifei Wu 1 2,  Zhilan Yan 1 2,  Lijun He 1 2,  Shufei Wang 1 2,  Haohao Hu 1 2,  Eyleen L K Goh 3,  Yingjie Zhu 4 5,  Fanglin Guan 6 7,  Teng Chen 8 9
Affiliations

Affiliations

  • 1 College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, PR China.
  • 2 The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, PR China.
  • 3 Neuroscience and Mental Health Faculty, Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore, Singapore.
  • 4 Shenzhen Key Laboratory of Drug Addiction, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
  • 5 Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, PR China.
  • 6 College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, PR China. fanglingguan@163.com.
  • 7 The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, PR China. fanglingguan@163.com.
  • 8 College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, PR China. chenteng@xjtu.edu.cn.
  • 9 The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, PR China. chenteng@xjtu.edu.cn.
PMID: 35715487 DOI: 10.1038/s41380-022-01651-2
Abstract

Methamphetamine (METH) is a widely abused psychostimulant, whose hyper-rewarding property is believed to underlie its addictive effect, but the molecular mechanism regulating this effect remains unclear. We previously reported that decreased expression of a novel MicroRNA (miRNA), novel-m009C, is implicated in the regulation of METH hyperlocomotion. Here, we found that novel-m009C may be homologous to hsa-miR-604. Its expression is consistently downregulated in the nucleus accumbens (NAc) of mice when exposed to METH and cocaine, whereas significant alterations in novel-m009C expression were not observed in the NAc of mice subjected to other rewarding and psychiatric stimuli, such as sucrose, morphine and MK-801. We further found the substantial reduction in novel-m009C expression may be regulated by both Dopamine Receptor D1 (D1R) and D2 (D2R). Increasing novel-m009C levels in the NAc attenuated METH-induced conditioned place preference (CPP) and hyperlocomotion, whereas inhibiting novel-m009C expression in the NAc enhanced these effects but did not change the preference of mice for a natural reward, i.e., sucrose. These effects may involve targeting of genes important for the synaptic transmission, such as Grin1 (NMDAR subunit 1). Our findings demonstrate an important role for NAc novel-m009C in regulating METH reward, reveal a novel molecular regulator of the actions of METH on brain reward circuitries and provide a new strategy for treating METH addiction based on the modulation of small non-coding RNAs.

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