Ignite Creation Date:
2024-05-05 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00050219
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2002-11-29
Brief Title:
Role of Dopamine in Response to Alcohol
Sponsor:
National Institute on Alcohol Abuse and Alcoholism NIAAA
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Striatal Dopamine and Alcohol Risk
Status:
COMPLETED
Status Verified Date:
2004-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the role of the brain chemical dopamine in peoples 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 006 and 008 grams per deciliter 008 gdL 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 002 gdL When the alcohol level has declined to 002 gdL 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 002 gdL and will then be sent home in a taxi
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 006 and 008 grams per deciliter 008 gdL 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 002 gdL When the alcohol level has declined to 002 gdL 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 002 gdL and will then be sent home in a taxi
Detailed Description:
Some persons are more likely to develop alcoholism than others Understanding the difference between persons at high vs low risk of developing alcoholism could be important for both prevention and treatment strategies
Tolerance for the sedative effects of alcohol has been shown in young adults to predict development of alcoholism later in life The basis for this increased risk is unclear It may be that persons who tolerate alcohol well as young adults experience more of the rewarding effects of alcohol eg euphoria or that they experience less of the negative effects of alcohol eg sedation or some combination of the two Fortunately brain-imaging tools can shed light on the brains reward response mechanisms to alcohol Differences in the reward circuits of persons who experience a euphoric response to alcohol may help explain why some people go on to develop alcoholism while others do not Both human and animal research point toward a difference in the density of dopamine receptors in the striatum of alcohol-preferring and non alcohol-preferring subjects The following experiment is designed to examine the relationship between response to alcohol dopamine receptor density in the striatum and dopamine release in response to alcohol
We propose classification of subjects as low response or high response on the basis of their level of response to a controlled alcohol challenge in the laboratory using the established methods of Schuckit et al to gather systematic data on subjects response to alcohol Next baseline levels of dopamine D2 receptor density in mesolimbic reward circuits of subjects in each group would be assessed in the PET scanner by using the radioactive dopamine antagonist C-11 raclopride C-11 raclopride binds to D2 receptors which will provide a signal proportional to the number of D2 receptors present This will allow us to measure and compare the baseline D2 receptor density in high and low response groups Directly after obtaining this baseline D2 receptor measurement we propose administration of a controlled alcohol challenge Acute alcohol administration causes release of dopamine in the striatum and can dislodge a portion of the C-11 raclopride that was bound to D2 receptors This will allow us to compare high and low response groups for differences in the displacement of C-11 raclopride induced by dopamine release thereby providing a measure of dopamine release in response to alcohol
The data obtained will allow us to compare the response to alcohol of young adults who are high vs low responders It will also permit comparison of these groups in terms of baseline striatal dopamine receptor density and striatal dopamine release in response to alcohol
Results of this experiment may identify a physiological basis for the increased risk in some young adults for development of alcoholism It may also provide a model for further studies of the relationship between response to alcohol risk for developing alcoholism and brain reward mechanisms
Tolerance for the sedative effects of alcohol has been shown in young adults to predict development of alcoholism later in life The basis for this increased risk is unclear It may be that persons who tolerate alcohol well as young adults experience more of the rewarding effects of alcohol eg euphoria or that they experience less of the negative effects of alcohol eg sedation or some combination of the two Fortunately brain-imaging tools can shed light on the brains reward response mechanisms to alcohol Differences in the reward circuits of persons who experience a euphoric response to alcohol may help explain why some people go on to develop alcoholism while others do not Both human and animal research point toward a difference in the density of dopamine receptors in the striatum of alcohol-preferring and non alcohol-preferring subjects The following experiment is designed to examine the relationship between response to alcohol dopamine receptor density in the striatum and dopamine release in response to alcohol
We propose classification of subjects as low response or high response on the basis of their level of response to a controlled alcohol challenge in the laboratory using the established methods of Schuckit et al to gather systematic data on subjects response to alcohol Next baseline levels of dopamine D2 receptor density in mesolimbic reward circuits of subjects in each group would be assessed in the PET scanner by using the radioactive dopamine antagonist C-11 raclopride C-11 raclopride binds to D2 receptors which will provide a signal proportional to the number of D2 receptors present This will allow us to measure and compare the baseline D2 receptor density in high and low response groups Directly after obtaining this baseline D2 receptor measurement we propose administration of a controlled alcohol challenge Acute alcohol administration causes release of dopamine in the striatum and can dislodge a portion of the C-11 raclopride that was bound to D2 receptors This will allow us to compare high and low response groups for differences in the displacement of C-11 raclopride induced by dopamine release thereby providing a measure of dopamine release in response to alcohol
The data obtained will allow us to compare the response to alcohol of young adults who are high vs low responders It will also permit comparison of these groups in terms of baseline striatal dopamine receptor density and striatal dopamine release in response to alcohol
Results of this experiment may identify a physiological basis for the increased risk in some young adults for development of alcoholism It may also provide a model for further studies of the relationship between response to alcohol risk for developing alcoholism and brain reward mechanisms
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-AA-0042 | None | None | None |