Human Alcohol Seeking Despite Aversion

Not Applicable

Terminated

Brief Summary: Prolonged alcohol use results in drinking despite resultant problems and adverse consequences. The investigators propose to test a laboratory model of human seeking despite aversion to use as an early marker of disease onset, and as a tool for study of its neural functional substrates, and identification of effective treatments.

Detailed Description: The long-term goal for this project is to establish a model of alcohol seeking despite aversion (SDA) as a platform for the laboratory testing of novel pharmacologic and behavioral interventions that can be used among those with the highest risk, but who have yet to progress to treatment-resistant drinking. The objective of this application is to test SDA across multiple levels of analysis. The investigators consider SDA as an early marker of alcohol use disorder progression that is related to lifetime drinking history, alcohol use disorder risks, and brain physiology. The investigators have completed a pilot study demonstrating that SDA can be objectively quantified via an intravenous alcohol self-administration task, in which operant work for identical incremental alcohol rewards is paired with aversive stimuli. This preliminary data supports the central hypotheses that behavior in the SDA model is attributable to lifetime alcohol exposure, is related to alcohol use disorder risk factors and phenotypes, and reflects alterations in neural system function. In this project, SDA will be measured along with recent and lifetime drinking history, negative affect-based rash action (i.e. negative urgency, including action with respect to alcohol use), and self-rating of the effects of alcohol. The rationale for this work is that it would lead to the first objective, well-validated measure of SDA in humans.

Recruitment & Eligibility

Inclusion Criteria

Healthy men and women age 21-55
Range of lifetime alcohol drinking history from 25 kg to 500 kg, with preference for extremes, plus recent drinking at least 7 drinks/week (women) and 20 drinks/week (men)
Able to understand and complete questionnaires and procedures in English
Willing and able to tolerate iv placement
Right-handed (for fMRI Arm only)

Exclusion Criteria

Pregnant or breast-feeding
Seeking or in treatment for substance use disorder or under court ordered abstinence
Medications, medical disorders or conditions that could affect study outcome or subject safety
Positive urine drug screen for amphetamines/methamphetamines, barbiturates, benzodiazepines, cocaine, opiates, or phencyclidine
Positive breath alcohol (BrAC) reading on arrival at any study visit
Actively suicidal (within previous year)
Left-handed or ambidextrous (for fMRI Arm only)

Arm && Interventions

Group	Intervention	Description
Lower lifetime alcohol drinking	Aversive cue	Half of the participants will have a history of lower lifetime alcohol consumption; all will participate in both interventions (Aversive cue, Neutral cue).
Resting state connectivity	Neutral cue	Some participants will also complete a functional magnetic resonance imaging (fMRI) session to determine resting state connectivity. All participants in this Arm will have completed both of the iv alcohol self-administration sessions (Aversive cue, Neutral cue).
Higher lifetime alcohol drinking	Neutral cue	Half of the participants will have a history of higher lifetime alcohol consumption; all will participate in both interventions (Aversive cue, Neutral cue).
Higher lifetime alcohol drinking	Aversive cue	Half of the participants will have a history of higher lifetime alcohol consumption; all will participate in both interventions (Aversive cue, Neutral cue).
Lower lifetime alcohol drinking	Neutral cue	Half of the participants will have a history of lower lifetime alcohol consumption; all will participate in both interventions (Aversive cue, Neutral cue).
Resting state connectivity	Aversive cue	Some participants will also complete a functional magnetic resonance imaging (fMRI) session to determine resting state connectivity. All participants in this Arm will have completed both of the iv alcohol self-administration sessions (Aversive cue, Neutral cue).

Primary Outcome Measures

Name	Time	Method
The Effect of Exposure to Aversive Cues on IV Alcohol Self-administration	In two infusion sessions, to occur 5-14 days apart	Participants earn 2.5 min exposures to an increase in iv infusion rate (causing a prescribed increase in breath alcohol concentration (BRAC)) by completing repetitions of a constant attention button-pressing task (CAT). The task is designed so that the number of correct CAT trials required increases progressively from 1 (for the first drink) to 380 (for the 20th drink) on an accelerating scale. The dependent measure Breakpoint is defined as the cumulative number of correct and incorrect CAT trials completed when the last drink is earned; in the time allowed possible values ranged from 1 to 800. Effect of the Aversive cue was assessed by calculating a difference score (Breakpoint Aversive Cue-Breakpoint Neutral Cue); the range of possible difference scores was -800 to +800. A positive difference score indicates a higher breakpoint (more alcohol earned) in the Aversive Cue session; a negative number indicates a lower breakpoint (less alcohol earned).

Secondary Outcome Measures