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Alcoholism

Description
Alcoholism, also known as alcohol dependence, is a disease that includes the following four symptoms: craving, loss of control, physical dependence, and tolerance. Alcoholism is a chronic, progressive, and often fatal disease. The craving that an alcoholic feels for alcohol can be as strong as the need for food or water. An alcoholic will continue to drink despite serious family, health, or legal problems. Like many other diseases, alcoholism is chronic, meaning that it lasts a person's lifetime; it usually follows a predictable course; and it has symptoms. The chemistry of alcohol allows it to affect nearly every type of cell in the body, including those in the central nervous system.

Who is at Risk?

The risk for developing alcoholism is influenced both by a person's genes and by his or her lifestyle. Currently, researchers are working to discover the actual genes that put people at risk for alcoholism. Recent genetic studies have indicated that close relatives of an alcoholic are four times more likely to become alcoholics themselves. Your friends, the amount of stress in your life, and how readily available alcohol is also are factors that may increase your risk for alcoholism.

Sources: National Institute on Alcohol Abuse and Alcoholism, Nidus Information Services, Medical Network, Inc.

Tragedy of Alcohol Abuse Drives TSRI Researcher's Work
Problems related to alcohol cut across nearly all social, financial, and age-related strata. About a third of the approximately 40,000 traffic fatalities every year involve drunk drivers. Thousands more die each year from accidental or deliberate alcohol poisoning, and from alcohol-related degenerative conditions like gastritis, cardiomyopathy, and liver disease. Despite many years of independent study of the biochemistry and physiology systems and processes hypothesized to be involved in alcoholism, the mechanisms are still unclear. Currently, there is no cure for alcoholism. TSRI Professor George F. Koob, Ph.D. has been studying the neurobiology of alcohol and alcoholism for several years, and he has developed models of normal and excessive drinking to study the neurophysiological correlates of alcohol consumption. His studies start with the brain and the neurobiology of alcohol in the brain.

The National Institute of Alcohol Abuse and Alcoholism (NIAAA) has funded a multi-year consortium headed by Koob to identify the molecular basis of alcoholism. The aim of the Integrative Neuroscience Initiative on Alcoholism consortium grant is to address the basic science of alcoholism and to establish a platform upon which future treatments can be built. The grant supports the combination of physiological, molecular, and cellular models to derive the genetic and environmental factors that form the basis of individual differences in developing excessive drinking. Koob hypothesizes that there may be individuals who are at increased risk of becoming alcoholics because their genetic makeup causes them to have higher corticotrophin-releasing-factor (CRF) levels than normal. He also believes it's possible that he will find brain areas that code for certain proteins responsible for the individual differences that make 15 percent of the population vulnerable to alcoholism and/or that protect 85 percent.

Koob leads TSRI's Pearson Center for Alcoholism and Addiction Research in collaboration with Professor Barbara Mason, Ph.D., Director of TSRI's Division of Clinical Pharmacology.

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A Possible Method for Treating Alcoholism
A team of TSRI scientists has described the cellular mechanism underlying the brain's response to alcohol, which suggests a possible method for treating alcoholism. The work ties together the effect of the brain peptide corticotrophin releasing factor (CRF) with alcohol. Both appear to influence neurotransmission in the amygdale, the so-called pleasure center of the brain, by increasing the transmission of one particular neurotransmitter called gamma amino butyric acid (GABA).

The research, led by TSRI Professor George Siggins, Ph.D. suggests that compounds that block CRF receptors might be a potential new therapeutic for alcoholics, who struggle to stop drinking. In the study, when the scientists applied an antagonist of CRF, they found that alcohol no longer had an effect. Currently, there is no cure for alcoholism.

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Finding Molecular Answers to Alcoholism
In the laboratory, TSRI Associate Professor Cindy Ehlers, Ph.D. and her colleagues have been trying to uncover the mechanisms and neurobiology of alcohol in the brain. Ehlers' research also has a clinical side. She has been looking to address the problems related to alcoholism among American Indians, Mexican Americans and African Americans. Ehlers' clinical work in Native Americans involves both a long-term study of the risk factors that exist for children and a large genetic analysis of adults to determine the factors that contribute to the high rates of alcoholism.

Ehlers' research has led her to believe that alcohol dependence is substantially heritable, and the basis of inheritance is passed to children from their parents. Ehlers and her colleagues are looking for these genes. They recently did a genome scan, looking broadly across the DNA of large families in order to find markers in the DNA that may be linked to a susceptibility to alcoholism. They are now attempting to map these markers to a particular gene and to a physiological phenomenon, such as alcohol craving and the experience of alcohol withdrawal, and behavior patterns such as binge drinking. Ehlers and her colleagues found a few DNA sites on chromosomes 4, 15, and 16 that are related to alcoholism. The researchers are now in the process of conducting what is called an association study to identify the genes and to test to see if they are indeed related to risk of alcoholism. The end goal is to come up with strategies for targeting these genes – perhaps developing new drugs that could help with treatment.

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Scripps Research Study Supports Promise Of Gabapentin As Potential Therapy For Alcoholism
New findings from scientists at The Scripps Research Institute provide evidence that the drug gabapentin affects certain components of the alcohol addiction cycle in the brain, supporting the idea that the medication, which is approved by the U.S. Food and Drug Administration for treating seizures and pain, also holds potential for the treatment of alcohol dependence. The scientists found that gabapentin normalizes the action of certain brain cells altered by chronic alcohol abuse in an area of the brain known as the central amygdala, which plays an important role in fear- and stress-related behaviors, as well as in regulating alcohol drinking. In the study, alcohol-dependent rodents receiving gabapentin drank less alcohol. Scripps Research Assistant Professor Marisa Roberto, Ph.D., was first author of the study. The exciting research results show that gabapentin not only changes the alcohol-consumption patterns of addicted rats (and not of the control group), but also may reverse some of the effects of addiction on a specific neurotransmitter in the brain.

This is an example of the strength of the translational approach of the Pearson Center for Alcoholism and Addiction Research at Scripps Research, where the clinical uses of gabapentin led scientists to hypothesize that gabapentin may act to restore homeostatic dysregulation of the GABAergic system. Cellular and behavioral studies converged to suggest that indeed gabapentin could normalize GABAergic tone in a specific brain region known to be dysregulated in dependent animals. Such results provide a strong rationale for translating these observations back to the clinical setting for the treatment of alcoholism. The scientists plan to further explore the mechanism of action of gabapentin in the brain. In addition, clinical trials on the effectiveness of gabapentin as a treatment for alcohol dependence are currently under way at The Scripps Research Institute.

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Scripps Research Study Overturns Decade-Old Findings In Neurobiology And Suggests Potential Target For Drugs To Combat Alcohol Addiction
In findings that should finally put to rest a decade of controversy in the field of neurobiology, a team at The Scripps Research Institute has found decisive evidence that a specific neurotransmitter system—the endocannabinoid system—is active in a brain region known to play a key role in the processing of memory, emotional reactions, and addiction formation. The new study also shows that this system can dampen the effects of alcohol, suggesting an avenue for the development of drugs to combat alcohol addiction.

This study will have a big impact in the field. It is the first time a study has shown a direct cellular interaction between endocannabinoids and alcohol in the brain. Scripps Research Associate Professor Marisa Roberto Ph.D., was first author and Paul Schweitzer, Ph.D., associate professor of the neurobiology of addiction at Scripps Research was the corresponding author.

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