Drinking, Anxiety, and Brain Chemicals, August 6, 2006

A brain protein that sustains nerve cells also regulates anxiety and alcohol consumption in rats, researchers from the University of Illinois at Chicago report in a study in the Aug. 9 issue of the Journal of Neuroscience.

In previous studies, the UIC researchers had first identified a gene that controls anxiety and alcohol consumption.

"We knew that gene, called CREB, controls the expression of a number of important genes in the brain," said Dr. Subhash Pandey, professor of psychiatry and anatomy and cell biology at UIC and Jesse Brown VA medical center and lead author of the paper. In the new study, they showed that a protein made by one of those CREB-controlled genes affects anxiety and drinking behavior depending on its level in two areas of the brain.

Pandey and his colleagues injected DNA of complementary sequence to the gene of the protein, called brain-derived neurotrophic factor (BDNF), into the brains of rats to block the gene from expressing BDNF. The "anti-sense" DNA was injected into three areas of the amygdala, an area of the brain associated with emotion and fear.

The researchers found that when levels of BDNF in the central and medial areas of the amygdala were lowered, anxiety and alcohol consumption increased. Decreased levels of BDNF in the third area, called the basolateral amygdala, had no effect.

When levels of BDNF in the central and medial amygdala were restored to normal by injecting BDNF, anxiety and alcohol consumption diminished.

The researchers measured anxiety by observing the rat's exploratory behavior in a maze. Alcohol consumption was measured by offering the animals one drinking bottle with water and one with alcohol, and noting the proportion of alcohol imbibed.

BDNF plays a vital role in the growth and maintenance of neurons. Many human studies have suggested that variations in the BDNF gene may be associated with alcoholism and anxiety disorders, Pandey said.

"In people, alcoholism is very frequently associated with anxiety disorders," he said. "And it is well established that high levels of anxiety promote alcohol consumption and also play a crucial role in relapse to alcohol drinking."

Pandey said the new research may suggest a target for drugs to treat or prevent anxiety and alcoholism.

"Our study suggests a molecular, neurochemical mechanism in the amygdala which may be responsible for the association of high levels of anxiety with excessive alcohol-drinking behavior," he said.