The Effect of Ethanol on Brain Activity

This study is designed to answer four questions:

• Which brain regions are activated in humans by the rewarding properties of ethanol administration?
• How does ethanol administration affect the brain response to visual cues known to evoke positive or negative emotion?
• Do individuals who regularly drink in ethanol in large amounts (heavy drinkers) differ from individuals who do not regularly drink large amounts of ethanol (social drinkers) in how ethanol affects brain function?
• Does ethanol administration affect the brain regions activated in a risk-taking task in social drinkers and heavy drinkers?

In order to determine which brain regions are activated by the rewarding properties of ethanol administration, we propose to use Blood Oxygenation Level Dependent (BOLD) fMRI techniques to test the hypothesis that during the time of rising and peak BAC, mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain will show significant increases in cerebral blood flow. Healthy, subjects who are not seeking treatment for an alcohol use disorder will be given intravenous (IV) ethanol or placebo infusions on separate days. An ethanol infusion will delivered at rates calculated to produce a BAC of 0.08 plus or minus. An ethanol infusion will delivered at rates calculated to produce a BAC of 0.08 plus or minus 0.005 g/dl at 15 minutes. Then the rate of the infusion will be adjusted so that for the next 30 minutes (second phase) BAC will be maintained at the target level of 0.08 0.005 g/dl. On the placebo day, subjects will receive a saline infusion at the same set of rates as used during their ethanol infusion. Continuous multi-slice fMRI data will be collected during each infusion. During each infusion, BOLD response to visual stimuli designed to evoke emotion will also be examined. In addition, we will compare the BOLD response of healthy social drinkers to that of healthy heavy drinkers. We will also compare the BOLD response elicited by risk-taking during the ethanol infusion to that during the placebo infusion in both social and heavy drinkers.

• INCLUSION CRITERIA LIGHT DRINKERS:

• in good health.
• between 21 and 45 years of age.

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• Currently consuming between 1 and 14 drinks per week.

Exclusion criteria

LIGHT DRINKERS:

• have an abnormal physical exam and/or have laboratory values outside of normal ranges;
• have fulfilled DSM-IV criteria for ethanol or other substance dependency (excluding nicotine) at any time;
• have fulfilled DSM-IV criteria for a current or past major psychiatric disorder (DSM-IV Axis I) or who have ever had a head injury requiring hospitalization.
• are over or under 20% of ideal body weight;
• have taken any prescribed, non-prescribed, or over-the-counter medications or drugs within 14 days prior to the study days (excluding oral contraceptive agents);
• are pregnant;
• report to have a "facial flushing" response to the consumption of ethanol;
• have never consumed at least two standard drinks of ethanol within one hour.
• have ferromagnetic objects in their bodies, which might be adversely affected by MRI (e.g., surgical clips, metal fragments in or near brain, eye or blood vessels, cardiac or neurological pacemaker, cochlear or eye implant). Any doubt about presence of these objects will result in exclusion from this study.
• Additionally, subjects will be asked to abstain from ethanol for at least 2 days prior to the studies.
• Regular tobacco users will be excluded from the study in order to avoid nicotine withdrawal symptoms. Occasional (not daily) use of tobacco products is acceptable.

Inclusion criteria

HEAVY DRINKERS:

• in good health.
• between 21 and 45 years of age.
• currently consuming between 20 and 40 drinks per week.
• not regularly abstinent for more than 3 days per week, but have abstained from alcohol for 3 consecutive days without experiencing withdrawal symptoms.
• able to provide a plausible history that they can abstain from alcohol without significant withdrawal symptoms when coming to the clinic. In addition, each participant will be asked to quantify their worst withdrawal symptoms using the Clinical Institute Withdrawal Assessment (CIWA) Instrument. Participants who score 8 or above will not be enrolled in the protocol.
• not seeking treatment for their alcohol consumption.

Exclusion criteria

HEAVY DRINKERS:

• have an abnormal physical exam and/or have laboratory values outside of normal ranges;
• have fulfilled DSM-IV criteria for any substance dependency (excluding alcohol or nicotine) at any time;
• have fulfilled DSM-IV criteria for a current or past major psychiatric disorder or who have ever had a head injury requiring hospitalization.
• are over or under 20% of ideal body weight;
• have taken any prescribed, non-prescribed, or over-the-counter medications or drugs within 14 days prior to the study days (excluding oral contraceptive agents);
• are pregnant;
• report to have a "facial flushing" response to the consumption of ethanol;
• have never consumed at least two standard drinks of ethanol within one hour.
• have ferromagnetic objects in their bodies, which might be adversely affected by MRI (e.g., surgical clips, metal fragments in or near brain, eye or blood vessels, cardiac or neurological pacemaker, cochlear or eye implant). Any doubt about presence of these objects will result in exclusion from this study.
• Additionally, subjects will be asked to abstain from ethanol for at least 2 days prior to the studies.
• Regular tobacco users will be excluded from the study in order to avoid nicotine withdrawal symptoms. Occasional (not daily) use of tobacco products is acceptable.