Nicotinic Receptor Genetic Variation and Alcohol Reward

Background: People with the brain disease AUD (alcohol use disorder) have a serious problem with drinking. Researchers want to study how different people react to alcohol, and how genes affect this. They will focus on a nicotine receptor gene that may increase a person s AUD risk. Objectives: To see if people with variations of a nicotine receptor gene take alcohol differently and have different brain responses to alcohol cues. Eligibility: Healthy adults ages 21 - 60. This study includes smokers and non-smokers. Design: Participants will be screened under another protocol. Participants will have three 9-hour visits. They must have no alcohol or non-prescription drugs before all visits and no food or drink before 2 visits. At every visit, participants will: - Get a light meal - Have breath and urine tests - Get taxi rides there and back At visits 1 and 3, participants will: - Have a thin plastic tube inserted in an arm and connected to a pump for alcohol infusion. - Have sensors on their chest to monitor heart rate. - Sit in a chair for 2.5 hours and get alcohol by pushing a button. Their breath alcohol level will be monitored. - Answer questions about mood and effects of alcohol - Give blood samples - Relax at the clinic while their breath alcohol level drops At visit 2, participants will: - Answer questions and do computer tests - Have an alcoholic drink and a snack - Have a magnetic resonance imaging (MRI) scan. They will lie in a machine that takes pictures of the brain. They will do computer tasks. - Have another drink and snack - Relax until their alcohol level drops Participants will have a follow-up call after each visit.

NCT03294460 Alcohol Drinking

MeSH:Alcohol Drinking

3 Interventions

Name: Alcohol (Oral)

Name: Alcohol (IV)

Name: Alcohol (Ethanol)

Purpose: Basic Science

Allocation: Non-Randomized

Single Group Assignment

There is one SNP

SNPs

1 rs16969968

To examine the effect of CHRNA5 (rs16969968) genetic variation on neural correlates of incentive salience for alcohol, as measured by BOLD response during the Alcohol-Food Incentive Delay (AFID) task using fMRI.. null.

To examine the effect of CHRNA5 (rs16969968) genetic variation on IV alcohol self-administration, as measured by BrAC exposure (peak BrAC, number of infusions, time to binge-level) in non-smoking, non-dependent drinkers.. null.

To examine the effect of CHRNA5 (rs16969968) genetic variation on resting-state functional connectivity (rsFC) among brain regions.

associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum and extended amygdala in non-smoking non-dependent drinkers.. To examine the effect of CHRNA5 (rs16969968) genetic variation on the rate of IV alcohol self-administration, as measured by the preferred rate during the second IV-ASA session in non-smoking, non-dependent drinkers.. null.

There has been a great interest in examining variation in target genes that may play a mechanistic role in the expression of these endophenotypes, such the missense single-nucleotide polymorphism (SNP) in the gene encoding the 5 subunit of the nicotinic acetylcholine receptor (CHRNA5) - rs16969968.

Participants will be stratified into equally-sized groups based on their smoking status (smokers and non-smokers) and rs16969968 genotype: 1).

HPO Nodes