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  • Neurobiological research on alcohol addiction had grown, but no mechanistically novel medications have been approved in more than 15 years. Promising candidates have failed in development. What have we been missing?

    Three themes have emerged from our attempts to address this question. First, studying neurobiological mechanism in animal models at a group level may be unable to capture mechanisms that render a vulnerable minority of alcohol users prone to disease. Second, patients with alcohol addiction progressively choose alcohol over healthy rewards. The underlying mechanisms may be difficult to identify in animal models that use alcohol as the only reinforcer. Third, in patients, alcohol use continues despite adverse consequences, yet in commonly used animal models, self-administration only results in delivery of the reinforcer.

    Through a series of papers, these themes converge to a story, with the amygdala, and its GABA-ergic microcircuitry as key players.