A human laboratory model of alcohol satiety and the role of glucagon-like peptide 1

Background: Observations from behavioral pharmacology studies demonstrate that a drink of alcohol can either prime further consumption or promote satiety. However, the alcohol satiety construct remains unexplored. Glucagon-like peptide 1 (GLP-1) is an endogenous satiety signaling peptide associated with reduced intake of both food and drug consumption through dopamine inhibition. This dissertation aims to understand alcohol satiety through two behavioral pharmacology studies and a commentary on the clinical implications of satiety for addiction.Study 1: Healthy young adult heavy drinkers (N=42) were administered one priming drink (target BAC 30mg%) followed by five mini-drinks (target BAC 10mg% each, or alcohol-free control at separate counterbalanced sessions) at 15-minute intervals. A questionnaire developed to measure alcohol satiety was given after each drink along with measures of subjective response and craving. Naturalistic drinking was assessed for 7 days using a transdermal alcohol sensor. Linear mixed modeling revealed significant increases in alcohol satiety during paced drinking of both alcohol and control drinks. Craving, stimulation, and at-risk drinking status moderated satiety. Individuals with slower rise rates of alcohol exposure in the field reached significantly greater levels of satiety at faster rates in the lab. Laboratory modeling established face validity, and field data established ecological validity of the alcohol satiety construct. Study 2: Healthy young adult heavy drinkers (N=40) received a dietary supplement (10g Fibersol®-2 mixed with water and aspartame sweetener + 725mg decaffeinated green tea extract capsule) or a calorically matched placebo (Aspartame mixed with water + aspartame capsule) on separate counterbalanced sessions. Blood was sampled before and 40 minutes after supplement preload to measure plasma GLP-1. Subjective effects and alcohol attention bias were measured in response to a priming drink of alcohol. Compared to placebo, the supplement significantly increased GLP-1 and reduced alcohol attention bias. GLP-1 concentration negatively correlated with alcohol attention bias. Dietary stimulation of endogenous GLP-1 may reduce the incentive motivational properties of alcohol cues. Conclusions: Findings provide preliminary evidence for an alcohol satiety construct, and the role of GLP-1 satiety signaling in reducing alcohol incentive motivation. Treatments to strengthen satiety signaling may be effective at reducing the harms of binge drinking.