Cerebral Hemispheres 2

NEUROSCIENTIFICALLY CHALLENGED

NEUROSCIENCE MADE SIMPLER

Epigenetics and Alcoholism

April 9, 2008


Many of us, even those without alcohol problems, may feel more inclined to have a drink after a bad day, when stress is building up, or when we are trying to take our minds off of something that’s bothering us. This is one of the reasons alcohol is so popular: it has the ability to relieve anxiety and stress, at least while it’s being served (the next morning is another story). It’s also, however, one of the reasons alcoholism is so insidious. For an alcoholic, periods of alcohol withdrawal involve severe anxiety. When in the throes of this angst, it is extremely difficult for an alcoholic to avoid returning to what their brain has identified as the most efficient stress-reducer within their reach. A recent report in The Journal of Neuroscience indicates that this withdrawal anxiety may be due to changes in gene expression.

Previous research has pointed to the importance of a neuropeptide transmitter called neuropeptide Y (NPY) in managing anxiety, and in modulating alcohol consumption. Low levels of NPY, specifically in the amygdala, have been found in animals that have a preference for alcohol. Additionally, knockout mice who are engineered to lack NPY receptors exhibit an increased proclivity for alcohol.

The researchers involved in the current study wanted to determine how fluctuations in NPY occur. They found that NPY transmission in rats is influenced by transient changes in gene expression. These changes, known in biology as epigenetic processes (epi- meaning “in addition to”), involve chemical modifications of DNA that can alter gene expression, but don’t affect the actual DNA sequence of the organism. Thus, the gene expression is somewhat temporary (in that the DNA is not permanently altered), although how long it actually lasts depends on the specifics of the process.

DNA is wound around proteins called histones, and how tightly they are knitted together can affect gene expression epigenetically. There are enzymes that can loosen how tightly they are wrapped up, called histone acetyltransferases (HATs), and those that can tighten the packing, known as histone deacetylases (HDACs). HATs generally promote gene expression, while HDACs inhibit it.

The research team in this study found that exposure to alcohol decreased the activity of the gene inhibitors (HDACs) in rats’ amygdalas, leading to increased gene expression. This expression resulted in higher levels of NPY, and the corresponding low anxiety levels that alcohol is known for. Withdrawal, however, increased HDAC activity, reducing NPY levels, and causing a significant increase in anxiety behavior. When the group administered a drug that blocks HDAC activity, they were able to prevent observable anxiety from occurring during withdrawal.

This suggests that a possible future treatment for alcohol withdrawal could involve pharmaceuticals that inhibit HDACs. Removing the consuming anxiety caused by withdrawal would be a potent tool in the treatment of the disorder. And, studying epigenetic processes may be a fruitful method of finding treatments for addiction in general, as transient changes in brain function (which could be due to gene expression) seem to be involved in many cases.

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