Alcohol dependence linked to chemical deficit

Anxiety has long been linked to substance abuse. It is the key psychological factor driving the impulse to drink alcohol and one of the first symptoms of alcohol withdrawal.

Now, researchers at the University of Illinois at Chicago have discovered they can control the urge to drink in experimental animals by manipulating the molecular events in the brain that underlie anxiety.

The study is published in the current issue of Alcoholism: Clinical and Experimental Research, the nation’s premier journal covering substance abuse.

The researchers found that a particular protein in the amygdala — the area of the brain associated with emotion, fear and anxiety — controlled the drinking behavior of laboratory animals.

Rats that were chronically fed alcohol showed high levels of anxiety when alcohol was withdrawn from their diet. In the early phases of withdrawal, levels of the active form of a protein called CREB were low in certain areas of the amygdala.

However, when alcohol was present in the bloodstream, or when normal levels of active CREB were restored experimentally, anxiety behaviors in the alcohol-dependent animals vanished.

“Some 30 to 70 percent of alcoholics are reported to suffer from anxiety, and depression — drinking is a way for these individuals to self-medicate,” said Subhash Pandey, associate professor of psychiatry and director of neuroscience alcoholism research at UIC. “If we can control the psychological symptoms, perhaps we can help many of the millions of Americans who are victims of alcohol addiction.”

CREB, or cyclic AMP responsive element binding protein, when activated, regulates the manufacture of a brain protein called neuropeptide Y. Low levels of active CREB or of neuropeptide Y correlated with symptoms of anxiety and excessive alcohol consumption, the scientists found.

In normal rats, the researchers blocked production of neuropeptide Y. With lower levels of neuropeptide Y, the animals showed signs of anxiety and their alcohol consumption increased. When levels of neuropeptide Y were restored by infusing it into the central amygdala, the rats’ excessive drinking behavior ceased.

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

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

Other researchers involved in the UIC study were Adip Roy and Huaibo Zhang, postdoctoral research associates in psychiatry.