March 05, 2004
Molecular Mechanism Of Alcohol On Brain Suggests Addiction Treatment

Scripps Research Institute researchers have discovered part of one mechanism of how ethanol affects the brain.

Previous studies have also shown that alcohol enhances GABA neurotransmission in the amygdala, the so-called pleasure center of the brain. Interestingly, the brain corticotropin releasing factor (CRF) stress system also increases GABA transmission in the amygdala.

CRF is a common peptide in the brain that is responsible for activating the hypothalamic-pituitary-adrenal stress response and in the amygdala for activating sympathetic and behavioral responses to stressors. CRF is found in lots of different parts of the brain and is known to be involved in the brain in response to stress, anxiety, and depression.

Significantly, the CRF system also seems to be central to alcoholism, and scientists at Scripps Research and elsewhere have shown that CRF is involved in the transition from alcohol use to alcohol dependence. Scripps Research Professor George Koob and his colleagues found recently that levels of CRF increase in brains treated with alcohol. Other studies have shown that CRF levels increase when animals are withdrawing from alcohol as well—a situation analogous to an alcoholic's protracted abstinence.

In their latest paper, Siggins and his colleagues show, at the cellular level, how alcohol and CRF interact. When neurons are exposed to alcohol, says Siggins, they release CRF, and this causes the release of GABA in the amygdala. And when the CRF receptor is removed altogether (by genetic knock out), the effect of alcohol and CRF on GABA neurotransmission is lost.

Siggins and his colleagues say that this suggests a cellular mechanism underlying involvement of CRF in alcohol's behavioral and motivational effects. During withdrawal, CRF levels increase and these changes may persist for a long time.

It also suggests a possible way of treating alcoholism—using CRF antagonists, or compounds that block the effects of CRF. In the current study, when the scientists applied an antagonist of CRF, they found that alcohol no longer had an effect.

"Not only did the antagonists block the effect of CRF in enhancing GABA transmission, it also blocked the effect of alcohol," says Siggins. "The response was totally gone—alcohol no longer did anything."

An understanding of mechanisms by which ethanol acts on the brain will lead to better treatments of alcoholism. But an understanding of the various mechanisms by which ethanol intervenes in brain function will also lead to the identification of targets for drug development to develop treatments that will emulate some of the effects of alcohol while avoiding many of the harmful side effects.

It seems likely that in the next few decades a deeper understanding of how drugs cause addiction will lead to the development of effective treatments for many and perhaps even all forms of addiction. Addiction may become much less common as a result.

Share |      Randall Parker, 2004 March 05 03:39 AM  Brain Addiction

Joseph Yaroch said at March 5, 2004 9:17 AM:

This is a wonderful, serendipitous finding. I hope it works in clinical practice. CRF recentor antagonists are being developed for use as antidepressants. If they work for alcholism as well, it will be the first really effective pharmacological treatment for alcoholism since Antabuse -- and a lot safer.

I hope that any pharmaceutical company that is developing CRF receptor antagonists will do the appropriate clinical trials to get a formal indication for alcoholism treatment, so the HMO's won't give us a hard time prescribing them.

Robert E. Sinclair said at March 13, 2004 12:40 PM:

Finally, an approach I, as an engineer and an alcoholic, can accept. I hope this line
of inquiry bears fruit so that addiction can be effectively treated.

GITTINS said at May 29, 2008 10:20 AM:

Drug addiction or drug dependence is a serious health problem. In addition to the huge direct health costs, there are massive costs. The drugs of primary concern are the stimulants and alcohol, although nicotine addiction is also an important health issue. Reducing the extent of drug dependence is one of the major goals of medicine.

Addiction treatment and recovery resources for the addict and their families.

Balu Ravi said at May 30, 2008 7:08 PM:

Comprehensive resources for those looking for recovery from addiction.

Charlie said at April 27, 2011 12:40 PM:

Since the environment of the individual can trigger addiction, involvement from the patient's loved ones is extremely important in addiction treatment. Otherwise there's always the danger of relapses or regressions. The problem is usually more than just the individual and the environment she or he is in needs to be conducive to recovery as well. The patient is actually at his or her most vulnerable during the first stages of recovery and the family needs to support the healing process. Without family support, the individual may just give up and turn to substance abuse once again.

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