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 sug
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Contact: Sharon Butler
sbutler@uic.edu
312-355-2522
University of Illinois at Chicago
26-May-2004