Brain Protein 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 alcoholpreference (P rats), which were found to have high anxiety levels andconsume greater amounts of alcohol than alcohol non-preferring (NP)rats.

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

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

In P rats, but not in NP rats, alcohol was shown to reduce anxiety andincrease the levels of active CREB and neuropeptide Y in the centralamygdala. Pandey said that the P rats' preference for alcohol suggestedthey used alcohol to lessen their anxiety, a situation that is notuncommon in humans.

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

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

The findings implicate a deficit of CREB activity in the centralamygdala in those who are genetically predisposed to anxiety andalcohol drinking behaviors, Pandey said.

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

Other researchers in the study were Huaibo Zhang, Adip Roy, and TiejunXu, postdoctoral research associates in the UIC department ofpsychiatry.

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