Alcohol sensitivity and the Incentive Sensitization Theory of Addiction
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The Incentive Sensitization Theory of Addiction (ISTA; Robinson and Berridge, 1993) posits that certain individuals are at-risk for developing addictive patterns of behavior by virtue of hypersensitivity to the incentive-motivational properties of drugs that, over repeated administrations, translates to a bias toward drug-related cues, such that these cues begin to take on the incentive-motivational properties of the drug itself. ISTA has been developed and validated in a preclinical rodent model and the theory is difficult to test experimentally in humans. The purpose of the current study was to develop a paradigm to investigate the neural mechanisms by which low sensitivity to the acute effects of alcohol may confer risk for AUD in the context of ISTA. One hundred-six participants identified as high (HS) or low (LS) in alcohol sensitivity on the basis of a self-report questionnaire completed a novel incentive salience learning task (ISLT) where unconditioned stimuli (US; alcoholic beverage odors [AO], sweet odors [SwO], nonconsummable control odors [NcO]) were consistently predicted by conditioned stimuli (CS; colored squares) while EEG was recorded. Participants also completed an approach-avoidance task where CS from the ISLT task served as target stimuli. While neither group showed neural processing biases toward AO, LS (but not HS) individuals showed neural processing biases toward the AO-paired CS as evidenced by larger P3 and SPN toward the AO-CS as CS-US associations were learned. Further, LS (but not HS) individuals experienced increases in craving (i.e., "wanting") for alcohol, but the groups did not differ in pleasantness ratings (i.e., "liking") of AO over the course of the ISLT task. Taken together, these data provide evidence that LS individuals show increases in alcohol "wanting" but not "liking" over the course of repeated alcohol odor presentations and that as CS-US associations are learned, LS individuals show neural indices of incentive salience attribution to the AO-paired CS, providing evidence that LS individuals are more susceptible to the incentive sensitization processes posited by ISTA to be associated with addiction risk. These findings represent the strongest evidence to date of the translation of ISTA to a human model.