Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm

Abstract

The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use severity was associated with greater baseline negative affect, sedation, and craving but did not predict changes in any SR domain during the alcohol challenge. Alcohol use severity also predicted greater self-administration. Craving during the alcohol challenge strongly predicted self-administration and sedation predicted lower self-administration. Neither stimulation, nor negative affect predicted self-administration. This study represents a novel approach to translating preclinical neuroscientific theories to the human laboratory. As expected, craving predicted self-administration and sedation was protective. Contrary to the predictions of the Allostatic Model, however, these results were inconsistent with a transition from positively to negatively reinforced alcohol consumption in severe AUD. Future studies that assess negative reinforcement in the context of an acute stressor are warranted.

The Interplay Between Subjective Response to Alcohol, Craving, and Alcohol Self‐Administration in the Human Laboratory

“…These results are also consistent with our recent work demonstrating that craving consistently predicted subsequent self-administration in the laboratory, even in the context of a progressive ratio translational task (Bujarski et al, 2018).…”

“…The first pathway suggests lower levels of response to the sedative and unpleasant effects of alcohol, and the second suggests higher sensitivity to the stimulant and pleasurable effects of alcohol (King et al, 2011, Schuckit, 1994, Schuckit and Smith, 1996. A recent study by our laboratory found that craving for alcohol during alcohol administration was a robust predictor of subsequent self-administration, such that greater self-reported craving was associated with higher levels of self-administration (Bujarski et al, 2018). In the same study we found that alcohol-induced sedation was associated with lower levels of selfadministration (Bujarski et al, 2018), which is consistent with longitudinal findings indicating that sedation may be protective against the development of an alcohol use disorder (AUD) (King et al, 2014).…”

“…A host of models have been developed and validated, starting with basic paradigm of asking individuals to choose between alcoholic drinks or monetary reinforcement which has been well-applied to testing AUD medications (O'Malley et al, 2002, McKee et al, 2009. This paradigm has been modified to capture impaired control (Leeman et al, 2013) and more recently, an intravenous (IV) alcohol-self administration version has been used to test determinants of binge drinking in the laboratory (Gowin et al, 2017) as well as the effects of AUD severity and allostasis on self-administration (Bujarski et al, 2018). Insofar as alcohol selfadministration represents the most clinically relevant outcome in human laboratory models for AUD, the present study examines the associations between SR and alcohol-induced craving as within-subject determinants of alcohol self-administration.…”

To Infuse or Ingest in Human Laboratory Alcohol Research

“…The literature associating intravenous alcohol self‐administration paradigms with behavioral and clinical phenotypes is emerging. Intravenous alcohol self‐administration has been associated with family history of alcoholism (Zimmermann et al, 2009), drinking history (Bujarski et al, 2018; Stangl et al, 2017), including binge drinking (Sloan et al, 2019), AUD risk (Gowin et al, 2017), craving (Green et al, 2019; Wardell et al, 2015), personality traits (Stangl et al, 2017; VanderVeen et al, 2016), sex differences (Cyders et al, 2016; Plawecki et al, 2018b), pharmacologic targets or interventions (Suchankova et al, 2017), and risk genotypes (Hendershot et al, 2016, 2017; Plawecki et al, 2013; Sloan et al, 2018; Suchankova et al, 2017).…”

Alcohol Cue–Induced Ventral Striatum Activity Predicts Subsequent Alcohol Self‐Administration

“…In light of the emerging role of functional neuroimaging in predicting drinking behavior and AUD treatment outcomes, a remaining question is the nature of the relationship between neuroimaging task‐induced neural activation and widely utilized laboratory paradigms considered proximal to real‐world consumption, including self‐administration tasks. To date, several studies have examined relationships of response across different laboratory paradigms (i.e., subjective response and self‐administration) and have consistently identified that alcohol craving during intravenous alcohol administration mediates the relationship between alcohol‐induced stimulatory effects and subsequent oral alcohol consumption (Bujarski et al, 2018; Green et al, 2019; Wardell et al, 2015). While relationships across human laboratory paradigms are recently delineated, no studies have yet investigated whether alcohol cue–induced BOLD response is predictive of responses within laboratory self‐administration paradigms.…”