MicroRNA expression profile and functional analysis reveal that miR-382 is a critical novel gene of alcohol addiction

Authors

  • Jingyuan Li,

    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
    Current affiliation:
    1. UCLA David Geffen School of Medicine, Los Angeles, CA, USA
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    • These authors contributed equally to this work.
  • Jing Li,

    1. Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
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    • These authors contributed equally to this work.
  • Xiaojun Liu,

    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
    Current affiliation:
    1. Harvard Medical School, Boston, MA, USA
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  • Shanshan Qin,

    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
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  • Yanzhong Guan,

    1. Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
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  • Yuwei Liu,

    1. Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
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  • Yunhui Cheng,

    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
    Current affiliation:
    1. University of Michigan Medical School, Ann Arbor, MI, USA
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  • Xiuwen Chen,

    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
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  • Wen Li,

    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
    Current affiliation:
    1. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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  • Shenming Wang,

    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
    Current affiliation:
    1. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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  • Ming Xiong,

    1. Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
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  • Eldo V. Kuzhikandathil,

    1. Department of Pharmacology & Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
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  • Jiang-Hong Ye,

    Corresponding author
    1. Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
    • Corresponding author: Tel: +1 312 563 2563; Fax: +1 312 563 3552;

      E-mail: chunxiang_zhang@rush.edu

      Corresponding author: Tel: +1 973 972 4510; Fax: +1 973 972 4172;

      E-mail: ye@umdnj.edu

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  • Chunxiang Zhang

    Corresponding author
    1. Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA
    • Corresponding author: Tel: +1 312 563 2563; Fax: +1 312 563 3552;

      E-mail: chunxiang_zhang@rush.edu

      Corresponding author: Tel: +1 973 972 4510; Fax: +1 973 972 4172;

      E-mail: ye@umdnj.edu

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Abstract

Alcohol addiction is a major social and health concern. Here, we determined the expression profile of microRNAs (miRNAs) in the nucleus accumbens (NAc) of rats treated with alcohol. The results suggest that multiple miRNAs were aberrantly expressed in rat NAc after alcohol injection. Among them, miR-382 was down-regulated in alcohol-treated rats. In both cultured neuronal cells in vitro and in the NAc in vivo, we identified that the dopamine receptor D1 (Drd1) is a direct target gene of miR-382. Via this target gene, miR-382 strongly modulated the expression of DeltaFosB. Moreover, overexpression of miR-382 significantly attenuated alcohol-induced up-regulation of DRD1 and DeltaFosB, decreased voluntary intake of and preference for alcohol and inhibited the DRD1-induced action potential responses. The results indicated that miRNAs are involved in and may represent novel therapeutic targets for alcoholism.

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