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October 17, 2010
2:00:00 PM - 4:00:00 PM
Room Hall B1-Area M
miR-382 Is a Novel Regulator of Alcohol Addiction through Dopamine D1 Receptor and DeltaFosB Pathway
  **   Chunxiang Zhang, M.D., Ph.D., Jingyuan Li, M.D., Ph.D., Jing Li, M.D., Ph.D., Xiaojun Liu, M.D., Ph.D., Jiang-Hong Ye, M.D., Ph.D.
Anesthesiology, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, New Jersey
Regulation of gene expression is considered a plausible mechanism of drug addiction such as alcohol abuse, given the stability of behavioral abnormalities that define an addicted state. However, how these addiction-related genes are regulated is currently clear. MicroRNAs (miRNAs) are a novel class of endogenous, noncoding RNAs that negatively regulate over 30% of the genes in a cell. One miRNA is able to regulate its multiple genes and is functionally important as a transcription factor. We thus hypothesize that miRNAs may be involved in alcohol-mediated addiction-related gene regulation in the nucleus accumbens (NAc). In the current study, we found that miR-382 was downregulated in NAc of rats after treatment with alcohol (1 g/kg, ip) for one week. Computational analysis revealed that dopamine D1 receptor is a potential target gene of miR-382. Indeed, dopamine D1 receptor and its downstream molecule, DeltaFosB, which are two well-known addiction-related signaling molecules in NAc, were upregulated by alcohol. Interestingly, downregulation of miR-382 via its inhibitor increased the expression of dopamine D1 receptor and DeltaFosB. In contrast, the expression of dopamine D1 receptor and DeltaFosB was downregulated by adenovirus-mediated overexpression of miR-382. The effects of miR-382 on the expression of dopamine D1 receptor and DeltaFosB were further confirmed in cultured catecholaminergic neuronal cells (CAD cells). The results demonstrated for the first time that miRNAs such as miR-382 participates in alcohol addiction through dopamine D1 receptor and DeltaFosB pathway. miRNAs may represent novel, promising therapeutic targets for alcohol abuse.

From Proceedings of the 2010 Annual Meeting of the American Society Anesthesiologists.