ATLANTA- New imaging techniques developed at the University of Chicago are revealing the effects of alcohol and Prozac with new anatomic and physiologic specificity, and should prove useful in the development of new psychiatric drugs, reported researchers at the annual meeting of the American Association for the Advancement of Science.

A number of studies have already been done demonstrating where drugs are taken up within the brain. The new research goes one step further, showing how drugs alter the dynamics of regional brain activity. The researchers have shown that certain medications can produce profound effects far from the sites where drug and brain initially interact.

"We're less interested in the biochemical properties of these drugs--how they bind to a specific type of neuron or how long they remain in the brain--than in their behavioral consequences, how they change brain function," said Malcolm Cooper, M.D., associate professor of radiology at the University of Chicago and director of the research team. We want to measure how a drug alters the rate of activity within the various regions of the brain and to correlate those results with the subjects' mood or behavior."

Magnetic resonance imaging (MRI) can provide precise anatomical images of almost any part of the brain structure. Positron Emission Tomography can provide stunning images of dynamic functional brain activity. The University of Chicago team have developed a new software program that combines the best from both imaging techniques, correlating the functional information from PET-scan images of brain activity with anatomic details acquired by MRI scans.

The researchers observed a number of interesting findings regarding the effects of alcohol. Alcohol crosses the blood-brain barrier quite easily and is taken up equally throughout most parts of the brain. Yet alcohol has its strongest effects on brain activity only in specific regions, such as those that regulate movement. Alcohol's effects also vary widely from one person to the next.

The researchers recruited volunteers to consume alcohol and then undergo both MRI and PET brain scans. The data revealed that the volunteers who showed a particular enjoyment of alcohol's euphoric effects showed increased activity in a left-brain region known as the limbic area, which is associated with positive moods. The volunteers who did not enjoy the effects of alcohol showed decreased activity in that same region.

Prozac (fluoxetine) is a novel antidepressant drug which appears to work by binding to a serotonin producing neurons throughout the brain. Nonetheless, the drug produces very localized changes in brain activity, affecting both the hippocampus and amygdala within the limbic system. Interestingly, the drug markedly increased brain activity in this area in those who were suffering from depression, and significantly enhanced their moods, it had very little metabolic or psychological impact on normal research volunteers.

"There have been many previous attempts to study the effects of drugs on brain metabolism, but because the effects are quite subtle and subject to considerable individual variation, most researchers long ago abandoned this area."

The research team also relied on several newer analytical tools to better characterize their results. This included combining periodic mood assessment of each volunteer with a series of simple but distracting cognitive tasks during the testing period in order to minimize variation in the volunteers' moods. The researcher also attempted to reduce the impact of person-to-person variation by focusing on groups of volunteers rather than on individuals.

"We found a good deal of individual variation in the strength of drug effects, but very little variation in localization, and a strong correlation between the metabolic effects and in mood or behavior," said Cooper's colleague John Metz, Ph.D., research associate in psychiatry at the Chicago Medical Center.

The methods pioneered in the current research should aid in development of new mood-altering drugs and in determining the optimal doses of neuro-psychiatric drugs, notes Cooper:

"It can take months to assess the behavioral response to a drug. The current trend is toward using cocktails, a combination of psychiatric drugs, rather than single-drug therapies. So any method that can help us visualize the effects of these drugs alone and in concert should lead to better understanding and more rational use of these medications," he said.

Science Updates Index

What's News Index

Feedback