The neurobiological underpinnings of the pleasurable effects of alcohol are complex and not well understood but likely involve inherent brain reward pathways including opioidergic and dopaminergic circuits (45,46). In addition, neuroadaptations in gamma-aminobutyric acid–ergic, glutaminergic, and corticotrophin systems are also likely involved in critical changes in the reward circuitry due to repeated alcohol exposures (4). On a behavioral level, animal research indicates that alcohol, and other addictive substances, are reinforcing through approach behavior processes and psychomotor activation (15). Although translation to human research has been challenging (47,48), the observed sensitivity to hedonic (liking) and motivational (wanting) effects of alcohol, as well as stimulatory effects, may provide important clues for targeting research on neurobiological substrates. Heightened striatal and mesolimbic system activity likely underlie these rewarding and euphoric alcohol effects (49). Indeed, work by Volkow and colleagues (50) suggests that faster increases in dopamine correspond to more intense reinforcing effects of drugs, including alcohol. Whether long-term use depletes dopamine function and reduces alcohol sensitivity remains an empirical question.
