Alcohol use disorder (AUD) is associated with numerous consequences for the individual and society including psychological, occupational, and health consequences, as well as public safety harms and annual financial costs exceeding $223 billion in the US(1). Thus, identifying the mechanisms underlying the development and maintenance of AUD has become increasingly important for AUD prevention and treatment. Four leading neurobiological theories of the development of addiction include tolerance, sensitization, incentive-sensitization, and allostasis. These theories purport nervous system adaptations to repeated alcohol exposure underlie the progression of compulsive drinking and development of addiction but they lead to differential predictions about the nature of these responses over time. While these theories are crucial to our understanding of AUD, they are largely based on animal data and their predictions have not yet been directly tested in controlled longitudinal human studies. The present study provided the first comprehensive repeated evaluation of alcohol responses in at-risk drinkers to test these neurobiological theories of AUD progression.
