May 27, 2004
Genetic Variation Increases Alcohol Abuse In Mice

A partial knock-out of a gene increased anxiety and alcohol consumption in a strain of mice.

Alcoholism tends to run in families, suggesting that addiction, at least in part, has an underlying genetic cause. Now, researchers at the University of Illinois at Chicago have discovered a gene linked to alcohol dependency.

Laboratory mice deficient in the gene were found to consume excessive amounts of alcohol, preferring ethanol to water and evincing highly anxious behavior in a maze test.

Results of the study are published in the May 26 issue of the Journal of Neuroscience.

The gene the researchers investigated manufactures a protein called CREB, or cyclic AMP responsive element binding protein, which is known to regulate brain function during development and learning.

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

When CREB is activated, it regulates the production of a brain protein called neuropeptide Y. Low levels of active CREB or of neuropeptide Y correlate with symptoms of anxiety and excessive alcohol consumption, the scientists showed in a previous study.

In the present study, mice that had only one copy of the CREB gene -- healthy mice have two copies -- produced lower-than-normal levels of the CREB protein, neuropeptide Y and another compound in the brain linked with alcohol drinking (called brain derived neurotrophic factor).

The mice consumed about 50 percent more alcohol than normal littermates and showed higher baseline anxiety-like behaviors, as measured by a maze test.

Alcohol exposure reduced their anxiety, though less so than in normal mice, and increased levels of active CREB protein and neuropeptide Y in parts of the amygdala, the area of the brain associated with emotion, fear and anxiety.

Pandey speculated that the animals' preference for alcohol suggested they used ethanol to lessen their anxiety, a situation than is not uncommon in humans.

"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," Pandey said.

According to the National Institute on Alcohol Abuse and Alcoholism, an estimated 14 million Americans suffer from alcohol problems. Alcohol abuse costs the economy roughly $185 billion per year.

Other researchers involved in the study were Adip Roy, Huaibo Zhang and Tiejun Xu, postdoctoral research associates in the UIC department of psychiatry. The National Institute on Alcohol Abuse and Alcoholism and the U.S. Department of Veterans Affairs provided support.

The point the article makes about the cost of alcoholism is important. Suppose in the next 10 to 20 years truly effective treatments are developed for alcoholism and drug addiction. Literally hundreds of billions of dollars will be saved per year in everything from increased production at work, fewer car accidents, less crime, families that do not fall apart and yet other changes. The future economic value from research on addiction will pay for the cost of the research many times over.

A lot of alcohol and other drug abuse amounts to self medication for anxiety, depression, and other emotional problems. Therefore ideal treatments for alcohol and drug abuse would need to reduce the feelings that encourage abuse. Though not all drug and alcohol abuse is a result of pre-existing emotional problems. Brain exposure to drugs at key stages of brain development increases cravings for drugs. Therefore the drugs themselves create the structural changes in the brain that cause addiction and it is too simplistic to see all drug abuse as only the product of self-medication against previously existing emotional problems.

Share |      Randall Parker, 2004 May 27 01:44 PM  Brain Addiction

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