Over the past decades, important brain regions and neuronal circuits involved in the development of AUD have been identified (Koob and Volkow, 2016). One example is the mesolimbic reward system, which includes the ventral tegmental area (VTA) and nucleus accumbens (NAc). This system is a key component in the positively reinforcing effects of alcohol (Russo and Nestler, 2013). Alcohol-induced neuroadaptations within this circuit and other brain regions may produce an inability to self-regulate consumption of alcohol. As tolerance and dependence develop, neural systems in the extended amygdala participate in the development of negative affect during withdrawal (Koob and Mason, 2016). Impaired function of the prefrontal cortex (PFC) contributes to craving and preoccupation with alcohol, major drivers of relapse (Goldstein and Volkow, 2011). Several molecular targets specific to neuronal function are also implicated in alcohol action (Jaramillo et al., 2018; Mason, 2017; Mayfield et al., 2016). Despite the progress in our understanding of the neurobiology of AUD, there have been no new pharmacotherapies in more than a decade. The limited number of FDA-approved drugs available for AUD patients are only modestly effective and are under prescribed (Leclercq et al., 2017; Mason, 2017).
