The Effect of Ethanol on Brain Activity

Summary

This study is divided into two parts; each designed to answer a separate but related question:

Which brain regions are activated in humans by the rewarding properties of ethanol administration?

Is it possible to demonstrate a conditioned response to a stimulus paired with rising blood alcohol concentrations (BAC) in humans and can this response be observed in the brain using functional magnetic resonance images (fMRI) techniques?

Part 1. 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, non-alcoholic subjects will be given intravenous (IV) ethanol or placebo infusions on separate days. The infusions will have three phases. On each day, during the first phase a saline infusion will be used to measure basal brain blood flow. The second phase will be an ethanol infusion delivered at rates calculated to produce a BAC of 0.08 plus or minus 0.005 g/dl at 10 minutes. The rate of the infusion for the next 10 minutes (third phase) will be calculated to maintain BAC at the target level of 0.08 plus or minus 0.005 g/dl for the duration of the infusion. On the placebo day, subjects will receive a saline infusion at the same set of rates for phases two and three as used during their ethanol infusion. Continuous multi-slice fMRI data will be collected during each infusion.

Part 2. In order to investigate conditioned response to ethanol, three groups of healthy, non-alcoholic subjects will be given a series of IV infusions on separate days. The experimental group will receive ethanol infusion paired with a conditioned stimulus (CS) which will be presented while the BAC is rising. One control group (I) of healthy, non-alcoholic subjects will also be given a series of intravenous ethanol infusions on separate days, but these infusions will not be paired with a CS. The other control group (II) will be given only saline infusions during the CS presentation. After three training sessions, all three groups will undergo an fMRI scan during which the CS will be paired with saline infusion. This will allow the response to the CS alone to be observed. After 10 minutes of CS presentation, the ethanol infusion will begin and continue for another 15 minutes. Conditioned response (CR) will be demonstrated if the experimental group shows greater increase in BOLD signal than the control groups in motivation areas such as mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain in response to the CS while they receive the saline infusion. Control group II will also undergo an fMRI scan and will be given saline infusion followed by ethanol infusion during their last 15 minutes in the scanner to control for the non-specific effects of repeated infusions \& scans on BOLD response to ethanol. If we are able to produce a CR in brain regions associated with motivation, it may be possible to use this CR as an experimental model for human alcohol craving.

Conditions

• Healthy

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  lead NIH

Principal Investigators

• Daniel W Hommer, M.D. · National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Eligibility

Min Age

21 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2003-12-09

Completion

2012-12-17

Countries

• United States

Study Locations