• Energy Research

The biological mechanisms by which acute stress increases alcohol consumption are unclear. One potential mechanism is that stress acts by altering the pharmacological and subjective effects of alcohol. Acute stress produces a cascade of physiological and psychological effects, each with a distinctive time course. In this study, we investigated whether different phases of response to an acute stress alter the subjective effects of intravenous alcohol, by administering the drug at 2 different times after the stress.Healthy men (n = 25) participated in 2 sessions: 1 with the Trier Social Stress Test and the other with a nonstressful control task, each followed by infusions of intravenous alcohol (targeting 40 mg% in 5 minutes) and placebo. One group of participants received alcohol within 1 minute of completing the tasks (Alc0, n = 11), followed by placebo 30 minutes later. In the other group (Alc30, n = 14), the order of alcohol and placebo infusions was reversed. Subjective effects (i.e., anxiety, stimulation, want more) and physiological measures (heart rate, blood pressure, salivary cortisol) were measured before and at repeated intervals after the tasks and infusions.Stress did not change the subjective effects of alcohol in either group. However, when individual differences in alcohol responses were considered, stress differentially altered the stimulant-like and sedative effects of alcohol. Among individuals who exhibited predominantly stimulant responses to alcohol in the nonstressful condition, stress decreased the stimulant-like effects of alcohol and "wanting more." By contrast, among participants who did not report stimulation after alcohol in the control session, stress decreased the sedative effects and increased "want more." In addition, alcohol administered immediately after the Trier Social Stress Test dampened cortisol responses yet prolonged negative subjective responses to the stress.These findings demonstrate that there are bidirectional relationships between alcohol and stress. Alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual's pattern of response to alcohol. This study highlights the fact that stress-alcohol interactions vary among individual drinkers, suggesting that the effects of stress on motivation to drink alcohol may also differ between individuals.

Associations between alcohol and the places it is consumed are important at all stages of alcohol abuse and addiction. However, it is not clear how the associations are formed in humans or how they influence drinking, and there are few effective strategies to prevent their pathological effects on alcohol use. We used a human laboratory model to study the effects of alcohol environments on alcohol consumption. Healthy regular binge drinkers completed conditioned place preference (CPP) with 0 vs. 80 mg/100 mL alcohol (Paired Group). Control participants (Unpaired Group) completed sessions without explicit alcohol-room pairings. After conditioning, participants completed alcohol self-administration in either the alcohol- or no alcohol-paired room. Paired group participants reported greater subjective stimulation and euphoria, and consumed more alcohol in the alcohol-paired room in comparison to the no alcohol-paired room, and controls tested in either room. Moreover, the strength of conditioning significantly predicted drinking; participants who exhibited the strongest CPP consumed the most alcohol in the alcohol-paired room. This is the first empirical evidence that laboratory-conditioned alcohol environments directly influence drinking. The results also confirm the viability of the model to examine the mechanisms by which alcohol environments stimulate drinking and to test strategies to counteract their influence on behavior.

Alcohol subjective experiences are multi-dimensional and demonstrate wide inter-individual variability. Recent efforts have sought to establish a clearer understanding of subjective alcohol responses by identifying core constructs derived from multiple measurement instruments.The aim of this study was to evaluate the temporal stability of this approach to conceptualizing alcohol subjective experiences across successive alcohol administrations in the same individuals.Healthy moderate alcohol drinkers (n = 104) completed six experimental sessions each, three with alcohol (0.8 g/kg), and three with a non-alcoholic control beverage. Participants reported subjective mood and drug effects using standardized questionnaires before and at repeated times after beverage consumption. We explored the underlying latent structure of subjective responses for all alcohol administrations using exploratory factor analysis and then tested measurement invariance over the three successive administrations using multi-group confirmatory factor analyses.Exploratory factor analyses on responses to alcohol across all administrations yielded four factors representing "Positive mood," "Sedation," "Stimulation/Euphoria," and "Drug effects and Urges." A confirmatory factor analysis on the separate administrations indicated acceptable configural and metric invariance and moderate scalar invariance.In this study, we demonstrate temporal stability of the underlying constructs of subjective alcohol responses derived from factor analysis. These findings strengthen the utility of this approach to conceptualizing subjective alcohol responses especially for use in prospective and longitudinal alcohol challenge studies relating subjective response to alcohol use disorder risk.

AbstractThe mood‐altering properties of alcohol are a key motivation for drinking, and people commonly report that they drink alcohol to alleviate stress or to relax. To date, the neural processes associated with the self‐reported calming effects of alcohol are not well understood. Existing data imply that alcohol may target and disrupt activity within anterior insula (aINS) and amygdala‐based neural networks, which are regions implicated in threat detection and anxious responding. The aims of the current study were (1) to examine the acute effect of alcohol upon functional connectivity within aINS and amygdala circuits and (2) to assess relationships between alcohol effects on functional connectivity and self‐reported subjective mood. Healthy men and women (N = 39) who reported regular binge drinking completed a within‐subjects, double‐blind, placebo‐controlled pharmacological functional magnetic resonance imaging experiment with i.v. infusions of either alcohol or placebo. Infusion profiles were personalized for each participant and raised breath alcohol concentration to 80 mg percent. Before, during and after infusions, participants rated their subjective mood (stimulation, sedation and calm). Results showed that alcohol dampened functional connectivity between bilateral aINS seed‐regions‐of‐interest and the dorsal anterior cingulate cortex (dACC), key nodes of the salience network. Additionally, the more that alcohol reduced right aINS‐dACC functional connectivity, the calmer participants felt during alcohol administration. Alcohol had no effect on amygdala functional connectivity. These findings suggest that alcohol disrupts aINS‐dACC functional connectivity, which may impair detection and appraisal of emotionally salient information and relate to acute relaxing effects of the drug.

Background:  Varenicline (VAR) is a partial nicotinic receptor agonist that is an effective smoking cessation medication. Preliminary evidence indicates that it may also reduce alcohol consumption, but the underlying mechanism is not clear. For example, VAR may reduce alcohol consumption by attenuating its subjectively rewarding properties or by enhancing its aversive effects. In this study, we examined the effects of an acute dose of VAR upon subjective, physiological, and objective responses to low and moderate doses of alcohol in healthy social drinkers.Methods:  Healthy men and women (N = 15) participated in 6 randomized sessions; 3 sessions each with 2 mg VAR and placebo (PL) followed 3 hours later by a beverage containing PL, low‐dose alcohol (0.4 g/kg), or high‐dose alcohol (0.8 g/kg). Subjective mood and drug effects (i.e., stimulation, drug liking), physiological measures (heart rate, blood pressure), and eye tracking tasks were administered at various intervals before and after drug and alcohol administration.Results:  VAR acutely increased blood pressure, heart rate, ratings of dysphoria and nausea, and also improved eye tracking performance. After alcohol drinking (vs. PL), VAR increased dysphoria and tended to reduce alcohol liking ratings. It also attenuated alcohol‐induced eye‐tracking impairments. These effects were independent of the drug’s effects on nausea before drinking.Conclusions:  Our data support the theory that VAR may reduce drinking by potentiating aversive effects of alcohol. VAR also offsets alcohol‐induced eye movement impairment. The evidence suggests that VAR may decrease alcohol consumption by producing effects, which oppose the rewarding efficacy of alcohol.

Individuals who experience greater stimulation and less sedation from alcohol are at increased risk for alcohol-related problems. However, little is known regarding the neurobiological mechanisms underlying subjective response to alcohol. The current study examined the degree to which alcohol-induced brain activation correlates with ratings of stimulation and sedation, using a within-subjects, double-blind, placebo-controlled design. Participants (N = 34 healthy adults with no history of alcohol use disorder) completed three sessions: a calibration session to determine the duration of infusion needed to bring the breath alcohol to 80 mg/dl for each subject, and two counterbalanced fMRI sessions with placebo and alcohol administration. During the fMRI sessions, participants underwent 50 min scans, which included a 10 min baseline period, the IV infusion period needed to bring breath alcohol concentration (BrAC) to a peak 80 mg/dl (on the alcohol session), followed by a post-peak decline period. Participants rated their subjective stimulation and sedation at regular intervals throughout the scan. A priori VOI analyses showed that the time course of stimulation correlated with BOLD signal in the striatum. The time course of sedation did not correlate with BOLD signal in any VOIs. There were no correlations in primary visual cortex, which served as a control. These findings are the first to show that alcohol effects in the striatum are linked to the positive, stimulant-like effects of the drug and advance our understanding of the neurobiological mechanisms underlying individual differences in subjective responses to alcohol, and more broadly, risk for alcohol use disorders.