Alcoholism 'Remodels' Brain DNA
Main Category: Alcohol / Addiction / Illegal DrugsAlso Included In: Genetics; Neurology / Neuroscience; Anxiety / Stress
Article Date: 04 Apr 2008 - 4:00 PDT
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Reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in the alcohol withdrawal symptoms, particularly anxiety, that make it so difficult for alcoholics to stop using alcohol.
The finding is reported by researchers at the University of Illinois at Chicago and the Jesse Brown VA Medical Center in the April 2 issue of the Journal of Neuroscience.
DNA can undergo changes in function without any changes in inheritance or coded sequence. These "epigenetic" changes are minor chemical modifications of chromatin -- dense bundles of DNA and proteins called histones.
"This is the first time anyone has looked for epigenetic changes related to chromatin remodeling in the brain during alcohol addiction," said Dr. Subhash C. Pandey, professor and director of neuroscience alcoholism research at the UIC College of Medicine and the Jesse Brown VA Medical Center in Chicago, the lead author of the study.
Chemical modification of histones can change the way DNA and histones are wound up together. Histone acetyltransferases (HATs) are enzymes that add acetyl groups to histones and loosen the packing, promoting gene expression. On the other hand, histone deacetylases (HDACs) remove acetyl groups from histones, causing them to wrap with DNA more tightly, decreasing gene expression.
The UIC researchers had previously shown in an animal model that levels of neuropeptide Y in the amygdala modulate anxiety and alcohol-drinking behavior. In the new study, they looked at the HDAC activity, acetylation of histones, and expression of the genes for NPY in the amygdala and the anxiety-like behaviors associated with withdrawal from chronic alcohol use.
Pandey and his colleagues found that acute exposure to alcohol decreases HDAC activity; increases the acetylation histones; increases levels of NPY -- and reduced anxiety in the animals.
Conversely, anxiety-like behaviors during withdrawal in animals with chronic alcohol exposure was associated with an increase in HDAC activity and decrease in histones acetylation and NPY levels.
Importantly, blocking the observed increase in HDAC activity using an HDAC inhibitor during alcohol withdrawal brought up histone acetylation and NPY expression levels in the amygdala and prevented the development of anxiety-like behaviors.
"Our findings suggest that HDAC inhibitors may have potential as therapeutic agents in treating alcoholism," Pandey said.
The researchers also found that levels of a protein known as CREB binding protein, which has HAT enzymatic activity, were increased by acute alcohol but were decreased during ethanol withdrawal.
They concluded that the enzymes that are involved in remodeling of chromatin play an important role in the anxiety that accompanies alcohol withdrawal as well as in the anti-anxiety effects of acute alcohol use.
"We need new strategies to treat alcoholism that are directed toward the prevention of withdrawal symptoms," Pandey said. "Anxiety associated with withdrawal from alcohol abuse is a key factor in the maintenance of alcohol addiction."
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The research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism and the Department of Veteran Affairs. Rajesh Ugale, Huaibo Zhang, Lei Tang and Anand Prakash of UIC and the Jesse Brown VA Medical Center also contributed to the study.
For more information about UIC, visit http://www.uic.edu/.
Source: Jeanne Galatzer-Levy
University of Illinois at Chicago
Visit our alcohol / addiction / illegal drugs section for the latest news on this subject.
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Scientific Confirmation Of What We Knew.
posted by Peter O'Loughlin on 5 Apr 2008 at 6:39 amA most helpful piece of research which confirms the long held view that high levels of anxiety, together with the common occurrence of sleep deprivation, are a major contributor to relapse.
It is therefore vital, that those who are attempting to stop drinking are able to find ways in which anxiety can be alleviated, as the hypnotic, sedative effects of alcohol wear off.
Pharmacological Inhibitors that assist that process would obviously be welcome; however they could also repress the natural power of the unconscious mind to induce feelings of comfort and relaxation, which can be assisted with various techniques such as meditation and hypnosis.
Since meditation is a skill that takes time to learn and develop, it is likely to be more useful in maintaining comfortable or manageable levels of anxiety, as the period of abstinence grows and the cognitive abilities of the patient are, insofar as possible, restored
Hypnosis on the other hand induced by a skilled practioner can have an immediate, and lasting benefits.It has the distinct advantage of bringing about an immediate and natural state of relaxtion, with an initial duration of up to 24 hours, but which progressively becomes extended. Therefore it has the added advantage of removing the barriers to sleeping well, ie tension and anxiety.
Another advantage is, that the patient can learn to understand that all hypnosis is self hypnosis and that he already have the resources, and abilities needed to induce it at will. Like any other skill, it needs to be practised regularly in order to become compptent, but since it is a perfectly natural process akin to daydrreaming, most people have a natural ability for it.
The advantages of hypnosis over a chemicl inhibitor is that the patient feels empowered. as he gradually comes to realise that it is something that he can achieve entirely from his own natural resources. Together with the realisation that there is no need for any gimmicks such as having to wave an object back and forth whilst the patient focuses on it; nor is there any need for artificial vocal instruction, or so called guided imagery, or even visualisation, which so many people find difficult anyway.
All that is required is a comfortable chair, encouragement from the practioner to the patient to focus on their breathing, without making any attempts to change either the rythmn or the pattern of it. Both will occur naturally. All the patient has to do is simply to focus on his breathing and allow themselves to become aware of how it is slowing down, in its own way and in its own time.
As this process starts to occur, a skilled practioner will not use words such as relaxation, but rather words such as comfortable, safe and secure. thus removing any pressure from the client that he has got to try and relax.. the practioner will also tell the patient how well he ( the patient) is doing.
He will remind the patient that the natural process of the breathing slowing down, does not require any assistance from the patient ,or the practioner, since the unconscious mind has been taking care of the patients breathing from the time he was in the womb; that it already knows what it has to do together with how and when to do it, and that all the patient has to do is simply allow themselves to experience and enjoy the emerging feelings, which are his own natural ones.
There is of course much more that could be added, but since the objective is to bring about immediate, and then lasting changes; the process, to be totally successful, has to be conducted with consideration of where the patient is at,rather than where we would like him to be. In short we treat the addict not the addiction. However I do not for one moment doubt that pharmacotherapy would be much quicker, but, it is also true that any medication, not only has side affects, it is a substitute for nature's abilities and powers.
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