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Haven’t lost the positive feeling: a dose-response, oral alcohol challenge study in drinkers with alcohol use disorder

Abstract

Models of addiction are based on neurobiological, behavioral, and pharmacological studies in animals, but translational support from human studies is limited. Studies are lacking in examining acute responses to alcohol in drinkers with alcohol use disorder (AUD), particularly in terms of relevant intoxicating doses and measurement of stimulating and rewarding effects throughout the breath alcohol concentration (BrAC) time curve. Participants were N = 60 AUD drinkers enrolled in the Chicago Social Drinking Project and examined in three random-order and blinded sessions for subjective and physiological responses to a beverage containing 0.0 g/kg, 0.8 g/kg, and 1.2 g/kg alcohol. BrAC in the alcohol sessions at 60 min was 0.09 g/dL and 0.13 g/dL, respectively. Both doses of alcohol produced significant biphasic effects on subjective measures of stimulation, euphoria, reward (liking and wanting), sedation, and neuroendocrine and cardiovascular factors. Increased pleasurable effects of alcohol were pronounced during the rising limb-to-peak BrAC and sedating effects emerged during the declining limb. Alcohol dose-dependently increased feel drug ratings and rewarding effects at peak BrAC or early declining limb, and physiological responses at the rising limb. Thus, rather than the notion of an overall tolerance, results show an alcohol response phenotype characterized by sensitivity to alcohol’s stimulating, rewarding and physiological effects. The results of this study may aid in the conceptualization of alcohol addiction as a disorder characterized by the persistence of enhanced hedonic alcohol responses rather than chronic tolerance and reward deficiency.

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Fig. 1: Breath Alcohol Concentration (BrAC) Curves and Feel Drug Ratings as a Function of Dose and Time.
Fig. 2: Subjective Alcohol Responses as a Function of Dose and Time.
Fig. 3: Subjective and Physiological Alcohol Responses as a Function of Dose and Time.

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Acknowledgements

The authors would like to extended appreciation to Patrick McNamara for project coordination, Nandini Kaluvakolanu for running the salivary cortisol assays, Jon Grant, M.D. for medical supervision and oversight, and Patrick Smith, Eric Giger, and James Faria for their role in data collection and database management. This research was supported by grant R01-AA013746 (AK) from the National Institute on Alcohol Abuse and Alcoholism and T32-DA043469 (AV) from the National Institute on Drug Abuse.

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AK conceived of the study design, supervised collection, management, analysis, and interpretation of the data, and led the drafting and final approval of the paper. AV substantially contributed to data interpretation and paper writing. MH and AF drafted sections of the paper and contributed to presentation of the results. DC provided statistical support. Authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Andrea C. King.

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King, A.C., Vena, A., Howe, M.M. et al. Haven’t lost the positive feeling: a dose-response, oral alcohol challenge study in drinkers with alcohol use disorder. Neuropsychopharmacol. (2022). https://doi.org/10.1038/s41386-022-01340-2

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