2. Academic Validation
  3. MicroRNA-132/212 negatively modulates opioid reward by targeting dopamine transporter in the ventral tegmental area

MicroRNA-132/212 negatively modulates opioid reward by targeting dopamine transporter in the ventral tegmental area

  • Transl Psychiatry. 2026 Feb 25;16(1):152. doi: 10.1038/s41398-026-03915-9.
Jie Meng # 1 2 3,  Zhonghao Li # 2,  Yi Zhang 4 5 6,  Dajun Zhang 7,  Haiting Liu 4 7,  Xiangyang Zang 2,  Yaqiong Zhao 2,  Jing Wen 4 7,  Wei Shu 8,  Xiaoke Nan 9,  Xianchan Li 9,  Yan-Xue Xue 10,  Xiaojian Jia 11 12 13
Affiliations

Affiliations

  • 1 The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
  • 2 National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China.
  • 3 Department of Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing, 100005, China.
  • 4 Shenzhen Kangning Hospital & Shenzhen Mental Health Center, Shenzhen, 518118, Guangdong, China.
  • 5 Clinical College of Mental Health, Shenzhen University Health Science Center, Shenzhen, 518118, Guangdong, China.
  • 6 Affiliated Mental Health Center, Southern University of Science and Technology, Shenzhen, 518118, Guangdong, China.
  • 7 School of Pharmacy, Shenyang Medical College, Shenyang, 110034, China.
  • 8 Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, No.45 Changchun Street, Xicheng District, Beijing, 100053, China.
  • 9 State Key Laboratory of Natural and Biomimetic Drugs and Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
  • 10 National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China. [email protected].
  • 11 Shenzhen Kangning Hospital & Shenzhen Mental Health Center, Shenzhen, 518118, Guangdong, China. [email protected].
  • 12 Clinical College of Mental Health, Shenzhen University Health Science Center, Shenzhen, 518118, Guangdong, China. [email protected].
  • 13 Affiliated Mental Health Center, Southern University of Science and Technology, Shenzhen, 518118, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 41741420 DOI: 10.1038/s41398-026-03915-9
Abstract

Addictive drugs, notably opioid drugs, have significant societal implications, yet the cellular and molecular mechanisms underpinning rewarding effects remain largely elusive. Noncoding transcripts, including the MicroRNAs (miRNAs), are pivotal regulators of diverse biological functions. Notably, the MicroRNAs miR-132 and miR-212, arising from a shared noncoding transcript, have links to several psychiatric conditions, including cocaine addiction. However, their contribution to opiate rewarding remains speculative. In this study, we discovered that repeated morphine administration decreases the expression of miR-132/212 in the ventral tegmental area (VTA) and induces a concurrent upregulation of the Dopamine Transporter (DAT). Using a luciferase reporter assay, we found that the DAT coding gene, SLC6A3 mRNA 3'UTR, is a direct target of miR-132/212. These miRNAs negatively regulated both mRNA expression and protein levels of DAT in vitro. This was corroborated by in vivo studies which revealed that behavioral experiments using a morphine-induced conditioned place preference (CPP) paradigm showed that suppression of miR-132/212 in the VTA facilitated the formation of morphine-induced CPP. Conversely, overexpression of miR-132 attenuated morphine preference in male and female adult rats, as well as adolescents. In sum, our findings uncover a regulatory mechanism wherein miR-132/212 modulates morphine induced reward behavior by fine-tuning DAT expression at the posttranscriptional level, providing a potential therapeutic target of rewarding effects.

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