In summary, based on the background presented, we hypothesize that ethanol exposure during adolescence decreases the expression of α-MSH and hence MC4R signaling in the hippocampus, leading to a lower BDNF activity that causes dramatical changes in the brain (e.g., neuroinflammation, neuronal death and decreased neurogenesis) that predispose to maintain alcohol abuse until adulthood. The gene discussed is MC4R; the disease is alcohol abuse.