It is estimated that the number of alcohol dependant is over a million in Japan. Although a lot of study suggested candidates, certain mechanism underlying the development of alcohol dependence is still unclear. Our previous findings suggested that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS) may play role in the development of ethanol dependence. In the present study, we investigated the expression of TRUSS in ethanol depencence. Mice were treated with liquid diet containing ethanol for 7 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 7th 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.  The mice were killed by decapitation and the prefrontal cortex was dissected. The expression of TRUSS in prefrontal cortex was significantly increased in ethanol dependence. We next investigated the role of TRUSS in the development of ethanol dependence using TRUSS antibody. We observed that the treatment of TRUSS antibody, significant prevented in the development of ethanol dependence. In conclusion, our findings suggest that the TRUSS may regulate the development of ethanol dependence.