One way to examine vulnerability to AUD is to characterize acute subjective responses to alcohol at different stages of development of the disorder (9). Two large prior studies found that greater initial stimulation and reward responses to alcohol (10,11), as well as lesser intoxicating and sedating effects (12) predict future drinking problems through young adulthood. These acute responses may change with chronic heavy drinking, due to neuroadaptations that result in either tolerance or sensitization. Tolerance, or a diminished response to the same dose of a drug after repeated use, is a diagnostic criterion for AUD. Conversely, sensitization, or an increase drug effect with repeated exposure, has also been linked to addiction (13,14). Although both tolerance and sensitization are integral components of neurobiological theories of the development and progression of addiction (14–16), most of the empirical evidence is based on studies using animal models.
