Brain protein linked to alcoholism and anxiety

Researchers at the University of Illinois at Chicago have discovered that a protein found in the brain is genetically linked to alcoholism and anxiety.

Results of the study are published in the October issue of the Journal of Clinical Investigation.

The researchers studied rats selectively bred for high alcohol preference (P rats), which were found to have high anxiety levels and consume greater amounts of alcohol than alcohol non-preferring (NP) rats.

The researchers focused on a molecule called CREB, or cyclic AMP responsive element binding protein, which is thought to be involved in a variety of brain functions. When CREB is activated, it regulates the production of another brain protein called neuropeptide Y. The higher-imbibing P rats were found to have lower levels of CREB and neuropeptide Y in certain regions of the amygdala -- an area of the brain associated with emotion, fear and anxiety -- than their teetotaling NP cousins.

"This is the first direct evidence that a hereditary deficiency of CREB protein in the central amygdala is associated with high anxiety and alcohol-drinking behaviors," said lead researcher Subhash Pandey, associate professor of psychiatry and director of neuroscience alcoholism research at the UIC College of Medicine.

In P rats, but not in NP rats, alcohol was shown to reduce anxiety and increase the levels of active CREB and neuropeptide Y in the central amygdala. Pandey said that the P rats' preference for alcohol suggested they used alcohol to lessen their anxiety, a situation that is not uncommon in humans.

The researchers showed that if they used a chemical to stimulate CREB activity and neuropeptide Y levels in the central amygdala, they could decrease the anxiety and alcohol intake in P rats. Conversely, chemically blocking CREB and neuropeptide Y action in NP rats provoked anxiety-like behaviors and increased their alcohol consumption.

"Genetically high anxiety levels are important in the promotion of higher alcohol consumption in humans," said Pandey. "Drinking is a way for these individuals to self-medicate."

The findings implicate a deficit of CREB activity in the central amygdala in those who are genetically predisposed to anxiety and alcohol drinking behaviors, Pandey said.

According to the National Institute on Alcohol Abuse and Alcoholism, an estimated 18 million Americans suffer from alcohol problems. Alcohol and drug abuse cost the economy roughly $276 billion per year.

Other researchers in the study were Huaibo Zhang, Adip Roy, and Tiejun Xu, postdoctoral research associates in the UIC department of psychiatry.

The UIC study was supported by the National Institute on Alcohol Abuse and Alcoholism and the U.S. Department of Veterans Affairs.

From University of Illinois at Chicago

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October 4, 2005