Nicotinic Receptor Genetic Variation and Alcohol Reward
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Summary
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: Participation will be based on evaluation under the NIAAA natural history protocol (14-AA-0181) or a screening visit under this protocol. Participants will have two 9-hour visits. They must have no alcohol or non-prescription drugs before all visits and no food or drink before the first visit. At every visit, participants will: * Get a light meal * Have breath and urine tests * Get taxi rides there and back At visits 1, 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.
Description
Objectives: Alcohol use disorder (AUD) is a chronic disease that has a tremendously negative impact on individuals and their families and a substantial burden on society. Research on quantitative endophenotypes such as alcohol response, and their genetic and environmental determinants, is critical to understanding the risk for AUD. 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 acetylcholi…
Eligibility
- Age range
- 21–60 years
- Sex
- All
- Healthy volunteers
- Yes
* This study will include healthy male and female participants from the general population prospectively genotyped to obtain balanced samples of four groups of participants based on their smoking status (smokers and non-smokers) and CHRNA5 rs16969968 genotype: 1). A-allele carriers (AA or AG genotype), and 2). G-allele homozygotes (GG genotype). The study will be open to all racial and ethnic groups, as long as the individual meets the genotype criteria. Inclusion and exclusion criteria will be evaluated from the data collected under the Natural History Protocol or screening update visit unde…
Interventions
- DrugAlcohol (Oral)
Oral Self-administration
- DrugAlcohol (IV)
IV Self-administration
- DrugAlcohol (Ethanol)
IV and Oral Self-administration
Location
- National Institutes of Health Clinical CenterBethesda, Maryland