Role of Metal Ion Transporter ZIP8 in Alcohol-Related Behaviors

Background: Alcohol use disorder (AUD) can damage people s health, work, and family. Researchers want to know more about why some people are more vulnerable to AUD than others. The ZIP8 gene may be linked to an increased risk of AUD. Researchers want to find out how different forms of the ZIP8 gene affect how healthy people drink alcohol and how alcohol affects their brain. Objective: To study how genes may affect how people drink alcohol and how it affects their brain. Eligibility: Healthy people aged 21 to 60 years. They must not smoke, and they must have no history of AUD. They must have European ancestry and be enrolled in Natural History Protocol (14-AA-0181). Design: Participants will have 2 study visits. At the first visit, participants will be given alcohol; it will be infused through a tube attached to a needle inserted into a vein. They may self-administer each dose by pressing a button. Over time, they will have to press the button an increasing number of times to receive more alcohol. The infusion period will last 2.5 hours. Participants will have blood samples taken and breath measurments, and they will do computer tasks and complete questionnaires during and after the infusion. After the infusion, they will remain in the clinic until their breath alcohol levels drop to a safe level. At the second visit, participants will have an imaging scan of their brain. They will do tasks and play games on a computer screen during the scan. Some participants may have an extra visit for screening. A mid-study visit may also be needed if more than 6 months pass between the 2 study visits.