Effects of Acute Plasma Tryptophan Depletion on Serotonin Receptor Occupancy and Binding Affinity Using PET in Healthy and Alcoholic Human Subjects

This study uses positron emission tomography (PET) scanning to study how serotonin works in alcoholics. Serotonin is a chemical that allows brain cells to communicate. There is evidence that people with alcoholism have altered serotonin; their brains begin to make and break down serotonin more slowly than people who do not drink. PET scans use radioactive substances injected into the body. A special camera detects the radiation emitted by the radioactive fluid and a computer processes the radioactivity into images of the brain, which show the activity of brain chemicals like serotonin.

People with alcohol dependency may participate in this study. Candidates are screened with a medical history, including questions about alcohol and drug use, physical examination, blood tests, breath alcohol tests, electrocardiogram (ECG), urine test for illicit drugs and, for women, a pregnancy test, and a stool test for hidden blood. They also undergo magnetic resonance imaging (MRI) scan of the brain and complete questionnaires on their alcohol and drug history.

Participants undergo the following tests and procedures:

• Diet low in tryptophan. Tryptophan is an amino acid from which serotonin is made.
• Brain MRI before starting the study to make sure brain structure is normal.
• Lumbar puncture (spinal tap) to collect a small sample of cerebrospinal fluid (CSF). A local anesthetic is given and a needle is inserted in the space between the bones (vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle.
• Arterial catheter (plastic tube) placed in an artery in the wrist area for drawing blood samples. The skin is numbed with a local anesthetic for placement of the catheter.
• Intravenous (IV) catheter placed in a vein for injecting the radioactive isotope used in the PET scan.
• Two PET scans - baseline and active.
• Amino acid drink (orange flavored) before the active PET scan. The drink lowers tryptophan levels.
• Amino acid capsules - 23 amino acid capsules are taken with the orange drink.
• Genetic analysis to help understand serotonin and alcoholism. A blood sample is collected for DNA testing and possibly establishment of a cell line (collection of cells that are grown in the laboratory from an original tissue specimen) for other genetic studies.

Patients are admitted to the intensive care unit for the lumbar puncture and arterial line procedures. After these procedures are complete, the patient is transferred by stretcher to the PET suite for scanning. During the two scans, blood samples are drawn from the artery and a small amount of CSF is collected each hour of the study. Each PET scanning session lasts about 3 hours. The study lasts 36 hours, during which time the subject remains in bed.