forensic autopsy cases. Alcohol dependence has spread worldwide, and the number of the patient is over a million in Japan. Although a lot of study suggested several candidates, certain mechanism underlying the development of ethanol dependence is still unclear. Several microRNAs (miRs) are highly expressed in the central nervous system and modulate the brain function via regulating gene expression. We have reported that acute ethanol administration caused the long-lasting increase in the expression of miR-124 in mouse brain. In the present study, we investigated the expression of miRs in mouse ethanol dependence model. Mice were treated with liquid diet containing ethanol for 10 days. Using the escalating ethanol dosage schedule, the mice were fed the ethanol diet as follows: 1st day: 1 w/v%; 2nd and 3rd day: 3 w/v%; 4th to 10th day: 4 w/v% ethanol diet, respectively. The control mice were given the same volume of ethanol-free liquid diet with sucrose substituted in isocaloric quantities for ethanol. The mice chronically treated with ethanol revealed severe withdrawal signs after discontinuation of ethanol. Total RNA was extracted from mouse limbic forebrain (containing nucleus accumbens). Comprehensive analysis of miRNA expression in ethanol dependence was performed by miRNA array. The miRNA array analysis showed 47 upregulated miRNAs in the ethanol dependence. Especially, miR-3063-3p highly upregulated (fold change >50) in ethanol dependence. Using target predictions of miRNA, we found histone deacetylase 7 as a target of miR-3063-3p. We found that the treatment of a class II histone deacetylase inhibitor trichostatin A during ethanol withdrawal significantly suppressed the ethanol induced rewarding effect. Our findings suggest that the upregulation of miR-3063-3p, resulting in the changes in histone deacetylase, has an important role in the development of alcohol dependence.