Acute Effects of Alcohol on PET Imaging of Phosphodiesterase-4B (PDE4B)
National Institute of Mental Health (NIMH)
Summary
Background: Phosphodiesterase-4B (PDE4B) is a protein in the brain that may play a role in several mental health disorders. Researchers want to know if drinking alcohol increases the binding of a radioactive tracer to PDE4B in the brain because of increased activity and/or amount of the protein. This knowledge may help create new ways to treat people with alcohol use disorder (AUD). Objective: To learn if alcohol increases PDE4B activity in the brain. Eligibility: Healthy people aged 21 to 70 years who drink socially but do not have AUD. They must be enrolled in protocol 14-AA-0181"NIAAA Natural History Protocol". Design: Participants will have up to 4 clinic visits with up to 3 imaging scans of the brain; these will include 1 or 2 positron emission tomography (PET) scans and 1 magnetic resonance imaging (MRI) scan. The first PET scan will be a baseline. Participants will receive a radioactive tracer through a tube inserted into a vein. A second tube will be inserted so that blood can be drawn during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. This visit will take about 6 hours. For the next PET scan, participants will receive alcohol (ethanol) through a tube in a vein until they have a blood alcohol concentration that is equal to the legal driving limit. This is the same as 4 or 5 drinks for most people. After the scan, participants must remain at the clinic for a few hours until their blood alcohol drops. This visit will take 14 to 16 hours. The MRI scan of the brain will take up to 2 hours in a separate clinic visit.
Description
Study Description: Alcohol drinkers with no history of AUD will be enrolled from protocols 14-AA-0181 or 000676. Using the PET radioligand \[18F\]PF-06445974 (Hereafter referred to as \[18F\]PF974) to measure PDE4B binding in the brain, 14-AA-0181 participants will be scanned twice: at baseline and following intravenous administration of ethanol to achieve a target breath alcohol concentration (BrAC) of 0.08 g% (80 mg/dL). For the ethanol condition, alcohol will be administered intravenously prior to PET acquisition to reach and stabilize the target BrAC. PET imaging will then be conducted wi…