Alcohol addiction is a chronic neuropsychiatric disorder that represents one of the most serious global public health problems. Yet, currently there still lacks an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs) have exhibited beneficial effects in a variety of neurological disorders, particularly in reversing behavioral deficits and neurotoxicity induced by prenatal alcohol exposure and binge drinking. In the present study, we investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on preventing relapse and alleviating withdrawal symptoms after chronic alcohol exposure. Our results demonstrated that fish oil significantly reduced the chronic alcohol exposure-induced aberrant dendritic morphologic changes of the medium-sized spiny neurons in the core and the shell of nucleus accumbens. This inhibited the expression of AMPAR2-lacking AMPARs and their accumulation on the post synaptic membranes of medium-sized spiny neurons and eventually alleviated withdrawal symptoms and alcohol dependence. Our study therefore suggests that N-3 PUFAs are promising for treating withdrawal symptoms and alcohol dependence.