To enhance our understanding of the etiology of AUDs, we need to examine AUD-associated DNA methylomic alterations in reward-related brain regions. Although, blood or saliva samples are easily accessible and blood or saliva DNA methylation changes can be valuable biomarkers for diseases including AUDs, the extent to which DNA methylation in the peripheral blood or saliva reflects that in the brain is not well established.95 Given that the reinforcing effects of alcohol are mediated through reward-related brain regions (eg, the ventral tegmental area, the nucleus accumbens, the prefrontal cortex, etc.), it would be desirable to investigate DNA methylomic changes in these brain regions of AUD subjects. Another possibility would be to investigate the epigenetics of these brain regions in animal models. In our recent study using DID mice as models discussed above, we examined alcohol-induced DNA methylation changes in the promoter region of Htr3a in nine reward-related brain regions of mice and showed a wide range of alterations in the methylation of this gene in different brain regions.96 These results indicate that DNA methylation can be tissue-specific. A small human
