Evidence for incentive salience sensitization as a pathway to alcohol use disorder.

The incentive salience sensitization (ISS) theory of addiction holds that addictive behavior stems from the ability of drugs to progressively sensitize the brain circuitry that mediates attribution of incentive salience (IS) to reward-predictive cues and its behavioral manifestations. In this article, we establish the plausibility of ISS as an etiological pathway to alcohol use disorder (AUD). We provide a comprehensive and critical review of evidence for: (1) the ability of alcohol to sensitize the brain circuitry of IS attribution and expression; and (2) attribution of IS to alcohol-predictive cues and its sensitization in humans and non-human animals. We point out gaps in the literature and how these might be addressed. We also highlight how individuals with different alcohol subjective response phenotypes may differ in susceptibility to ISS as a pathway to AUD. Finally, we discuss important implications of this neuropsychological mechanism in AUD for psychological and pharmacological interventions attempting to attenuate alcohol craving and cue reactivity.