title: MicroRNA expression profile and functional analysis reveal that miR-382 is a critical novel gene of alcohol addiction.
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.
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Rush University, Chicago, IL, USA.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Qin
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Guan
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Liu
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Xiong
authors.forename: Eldo V
authors.initials: EV
authors.lastname: Kuzhikandathil
authors.forename: Jiang-Hong
authors.initials: JH
authors.lastname: Ye
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D000431:Ethanol / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis
chemical_list: C483820:Fosb protein, rat; D035683:MicroRNAs; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D000431:Ethanol
keywords: DeltaFosB; alcohol addiction; dopamine receptor D1; miR-382; microRNAs