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Ramchandani, VA1, Stangl BL1, Vaughan CL1, Sloan ME1, Hendershot CS2

1: Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, USA.
2: Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Canada.

The neurobiological underpinnings of alcohol seeking and consumption can be broadly categorized into response domains that map onto the Research Domain Criteria of reward/salience, negative affect, and cognitive control. Human laboratory models of alcohol self-administration (ASA) can help characterize these response domains and their relationship with the risk for alcohol use disorder. This study aimed to characterize the relationship between measures of cognitive dyscontrol, specifically impulsivity and impaired control, on intravenous ASA (IV-ASA) exposure-response measures in non-dependent drinkers.
Participants (n=152) completed a free-access IV-ASA session where they could push a button to receive individually standardized alcohol infusions. Subjective response was measured serially using the Drug Effects Questionnaire (DEQ). IV-ASA measures included PEAK and AVG Breath-Alcohol Concentration (BrAC) and number of button presses (NBP). Impulsivity measures included Barrett’s Impulsivity Scale (BIS), UPPS-P Impulsive Behavior Scale, and the rate constant from the Delayed Discounting (DD) task. Drinking history was measured using the timeline followback (TLFB). A subset (n=32) completed the Impaired Control Scale (ICS), which assessed control over drinking.
Impulsivity and ICS measures were positively associated with TLFB. Individuals with higher ICS scores also had higher impulsivity scores. Those with higher impulsivity measures also had greater IV-ASA, and higher perceptions of liking and wanting more alcohol during both free access and PR sessions. Individuals with higher ICS scores also had greater IV-ASA, and higher subjective perceptions of liking and wanting more alcohol. Those who achieved binge-level BrACs during IV-ASA had heavier drinking histories, greater DD, lack of premeditation, and greater attempts to control their drinking in the past (all p’s<0.05).
These results suggests that impulsivity and impaired control moderate exposure-response relationships during IV-ASA in non-dependent drinkers, and may explain the potential significance of cognitive dyscontrol as a predictor of alcohol use and misuse, and as a target for interventions for reducing alcohol use. Ongoing work includes development of a novel IV-ASA paradigm to model loss-of-control over alcohol consumption in compulsive drinkers.