A neural circuit in the brains of mice controls the development of compulsive drinking disorders, according to a new study. The results identify a biomarker that could, if the findings translate to humans, become a target for therapies for alcohol use disorders. In our society, most people are exposed to alcohol - the most commonly abused substance - at some point in their life. Excessive alcohol use is linked to more than 200 diseases and is a leading cause of preventable death. However, even among those that drink regularly, only a small fraction develop a compulsive drinking disorder or addiction. Why some who drink to excess lose the ability to control their alcohol use despite the significant negative health and personal consequences while others do not is poorly understood. Although previous studies have suggested that preexisting and alcohol-induced changes in the prefrontal cortex (PFC) may contribute to compulsive substance use, these explanations fail to account for the variety of outcomes apparent in the development of compulsive drinking behavior among individuals who drink. Seeking to understand if individual brain differences could better reveal who becomes a compulsive drinker, Cody Siciliano and colleagues examined the brains of binge-drinking lab mice - all of whom had equal prior exposure to alcohol -before and after they drank alcohol compulsively. This is the "first time we've been able to longitudinally image neurons from the beginning of initial alcohol exposure all the way through the development of compulsive binge-drinking patterns," said author Kay Tye in a related video. The results revealed that a neural circuit from the medial PFC to the dorsal periaqueductal grey (PAG) of the brainstem plays a key role in triggering compulsive drinking, the authors say. What's more, the authors show that manipulation of the mPFC-dPAG circuit can both increase or decrease compulsion. While it remains to be seen if the findings translate to humans, effective treatments for alcohol use disorders are needed and Siciliano et al.'s findings offer an extremely promising step forward, write Kimberly Nixon and Regina Mangieri in a related Perspective.