Human Alcohol Seeking Despite Aversion

Study Overview
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Brief Summary
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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
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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 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.

Official Title
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Human Alcohol Seeking Despite Aversion

Conditions
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Alcohol Abuse

Intervention / Treatment
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* Behavioral: Aversive cue
* Behavioral: Neutral cue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Higher or lower lifetime alcohol drinking history Able to understand and complete questionnaires and procedures in English BMI between 18.5 and 32 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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2 session crossover, random order, single blind
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Higher lifetime alcohol drinking<br>Half of the participants will have a history of higher lifetime alcohol consumption; all will participate in both interventions (Aversive cue, Neutral cue). | Behavioral: Aversive cue<br>* Participants will be exposed to unpleasant pictures and tones during performance of a task to earn alcohol<br>Behavioral: Neutral cue<br>* Participants will be exposed to neutral pictures and tones during performance of a task to earn alcohol<br>|
| Other: Lower lifetime alcohol drinking<br>Half of the participants will have a history of lower lifetime alcohol consumption; all will participate in both interventions (Aversive cue, Neutral cue). | Behavioral: Aversive cue<br>* Participants will be exposed to unpleasant pictures and tones during performance of a task to earn alcohol<br>Behavioral: Neutral cue<br>* Participants will be exposed to neutral pictures and tones during performance of a task to earn alcohol<br>|
| Other: Resting state connectivity<br>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). | Behavioral: Aversive cue<br>* Participants will be exposed to unpleasant pictures and tones during performance of a task to earn alcohol<br>Behavioral: Neutral cue<br>* Participants will be exposed to neutral pictures and tones during performance of a task to earn alcohol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IV alcohol self-administration | Between session differences in self-administration will be evaluated using progressive work breakpoint | Within session |