Role of Dopamine in Response to Alcohol

Purpose

This study will examine the role of the brain chemical dopamine in people's response to alcohol consumption. Dopamine is thought to influence whether people have a strong or weak response to alcohol and how pleasurable that response is. The findings of this study may shed light on why some people are at higher risk of developing problem drinking behaviors.

Healthy normal volunteers between 21 and 25 years of age who have never had a serious problem with alcohol abuse or drug abuse may be eligible for this study. Candidates will be screened with a medical history and physical examination, and will be interviewed about their smoking and drinking behaviors. Participants will undergo test procedures on two separate days, as follows:

Test Day 1

Upon arrival at the Clinical Center, participants will take a breathalyzer test for alcohol and provide a urine sample for a drug screen. Women will also have a urine pregnancy test. They will then lie on a hospital bed and two intravenous catheters (IV lines) will be placed, one into each arm. One line will be used to collect blood samples during the test session; the other will be used to infuse alcohol into the bloodstream. The alcohol will rapidly increase the blood alcohol level to between 0.06 and 0.08 grams per deciliter. (0.08 g/dL is the level at which a person is charge with driving under the influence of alcohol in all States.) Before, during, and after the infusion, subjects will be asked about their feelings in response to the alcohol, such as confusion, elation, level of discomfort or dizziness, ability to concentrate, and so forth. At 35 and 60 minutes after the infusion begins, subjects will take a body sway test. This involves standing on a machine to determine how the alcohol has affected the sense of balance. Subjects will then relax in the clinic for a few hours. During this time, a blood sample will be collected and a questionnaire will be given hourly until the blood alcohol level has gone down to 0.02 g/dL. When the alcohol level has declined to 0.02 g/dL (usually 3 to 4 hours after the infusion), the subject will be sent home in a taxi.

Test Day 2

Participants will again take a breathalyzer test for alcohol and provide a urine sample for drug screen and, for women, a pregnancy test. Subjects will lie on a hospital bed and three IV lines will be inserted, one to draw blood samples, one to infuse alcohol, and one to give raclopride, a radioactive substance used for positron emission tomography (PET) scanning. For PET, the subject lies on a table in the scanner with a mask placed over his or her head to help hold the head still during the scan. After a brief scan to adjust the machine, a small amount of radioactive water (O-15 water) is injected through the IV line and a series of pictures is taken over a period of about 1 minute. These images show how the radioactive water distributes in the brain, indicating blood flow. After the water scan, raclopride is given through the IV line and more pictures of the brain are taken over the next 2 hours. Blood samples are collected during and after the raclopride scan. During this procedure, subjects are asked the same questions about their feelings in response to the alcohol as they did during the earlier session. After he scans, they will be monitored in the clinic with hourly blood tests and questionnaires until the blood alcohol concentration decreases to 0.02 g/dL and will then be sent home in a taxi

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