Protein Plays Key Role in Alcohol Abuse

Study finds it's the same one that dissolves blood clots

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By
HealthDay Reporter

MONDAY, Jan. 3, 2005 (HealthDayNews) -- A protein that plays a critical role in dissolving blood clots also appears to have a role in alcohol addiction.

Mice who lacked the protein, called tissue-plasminogen activator (tPA), were less likely to become physically dependent on ethanol, a derivative of alcohol, according to a new study.

This protein may play a role in dependence and on the sometimes violent withdrawal symptoms that alcoholics experience, the study authors said.

Researchers reporting in the Jan. 3-7 issue of the Proceedings of the National Academy of Sciences feel the findings may suggest new targets for drug therapies for alcoholism.

Alcohol addiction is an extremely complicated phenomenon affecting many parts of the brain.

"The problem with alcoholism is it pretty much effects everything in the brain -- all possible receptors and neurotransmitter systems -- and we don't know which are relevant for which," explained Dr. Adam Bisaga. He is an assistant professor of psychiatry at Columbia University and an addiction psychiatrist at the New York State Psychiatric Institute, both in New York City. Bisaga was not involved in the study.

There are two main receptors involved in alcohol addiction, called GABA and NMDA (N-methyl-D-aspartic acid). "In the past, we used to think GABA was where most of the effects of alcohol were, but recently NMDA has become much more of a focus," Bisaga said. "When we make animals physically dependent on alcohol, the NMDA receptor goes up."

Previous research had also suggested that tPA levels went up as a result of physical addiction to various opiates.

The authors of the new study wanted to see if tPA was related to any other aspects of addiction in the brain.

They looked at ethanol, which is often found in alcoholic beverages. People who are alcoholics frequently develop a tolerance to ethanol's effects and, when they quit abruptly, may experience seizures and other withdrawal symptoms that can be life-threatening.

The authors found that mice that were deficient in the gene that produces tPA that were made physically dependent on ethanol were less likely to go through withdrawal.

Conversely, an agent called ifenprodil blocked the effects of tPA in producing withdrawal seizures.

The findings indicate that tPA's interaction with the NMDA receptors is involved in withdrawal. Specifically, the authors believe the interaction between tPA and a subunit (NR2B) of the NMDA receptor may be responsible for promoting physical dependence on alcohol, including the symptoms of withdrawal.

The question is whether this new information has any therapeutic implications.

"Alcoholics are already dependent, so the question is whether this mechanism is also involved in other aspects of addiction," Bisaga said. "We're not yet at the point of preventing addictions. We have people who already are dependent. The question is how can we reverse that."

He added, though, that tPA may be involved in other effects of alcohol.

According to the American Heart Association, tPA is a clot-busting drug that's approved for use in certain patients having a heart attack or stroke.

More information

For more on alcoholism, visit the National Institutes of Health.

SOURCES: Adam Bisaga, M.D., assistant professor of psychiatry, Columbia University, and addiction psychiatrist, New York State Psychiatric Institute, New York City; Jan. 3-7, 2005, Proceedings of the National Academy of Sciences

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