Brain "Remodeling" Implicated in Alcoholism-Anxiety Link
> 4/4/2008 12:09:13 PM

For some alcoholics, anxiety may play a key role in both their initial drinking behaviors and their subsequent dependence, according to research from April's issue of the Journal of Neuroscience. Because alcohol can have an anti-anxiety effect, some people may begin drinking as a way to self-medicate. Alternately, the anxious behavior that occurs as a symptom of alcohol withdrawal can prevent many from overcoming their addiction. Researchers from the University of Illinois at Chicago have examined this subject in the past, and in a new study they build upon their previous work by examining chemical mechanisms that may be behind this connection.

The researchers focused their study on small chemical changes occurring in chromatin, which is involved in forming chromosomes during cell division and is composed of DNA and proteins known as histones. These changes, caused by enzymes, can alter a gene's function, or expression. Enzymes called histone acetyltransferases (HATs) add chemicals to histones, causing an increase in gene expression, while another kind of enzyme, histone deacetylases (HDACs), remove chemicals and cause reduced gene expression.

Previous work
by head research Dr. Subhash C. Pandey has pointed toward neuropeptide Y and CREB binding protein as genetic factors contributing to the relationship between anxiety and alcoholism, and this current study also supports this theory. Using rats, the researchers observed that short-term alcohol exposure reduced anxious behavior. This effect was accompanied by a decrease in HDAC activity and greater HAT activity, which led to an increase in CREB binding protein and in the expression of genes for neuropeptide Y. In addition, they discovered that the anxiety of rats abstaining from alcohol after long-term use was associated with increased HDAC activity and decreased HAT activity, which resulted in reduced levels of CREB binding protein and reduced expression in genes for neuropeptide Y. Importantly, using an HDAC inhibitor, they were able to prevent these alterations from occurring and cause a rise in  levels of neuropeptide Y and CREB binding protein, which in turn prevented anxiety in rats going through alcohol withdrawal.

The researchers stress the importance of new medications targeting alcohol withdrawal, as these symptoms hinder a significant portion of individuals from successfully abstaining. Medications that inhibit HDAC may be beneficial for some, and further study of the mechanisms at play should provide further insight into potential treatment options. As research continues to demonstrate the genetic processes involved in both alcohol dependence and anxiety, we will better understand the relationship between these behaviors and the most effective ways of helping those who struggle with both.

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