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Scientist Profile - George Koob

In Pursuit of Treatments for Alcoholism

"Most people in this country drink," says Scripps Research Professor George F. Koob, "yet only some become alcoholics. Why? That's the question we're trying to answer."

Koob 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 - some of which we understand, and some of which is only now coming to light.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recently funded a five-year, $38 million grant to support a consortium led by Koob. The multi-institutional group aims to identify the molecular basis of alcoholism, establishing a platform upon which future treatments can be built. Alcoholism, a chronic disease characterized by compulsive use of alcohol and loss of control over alcohol intake, is devastating both to individuals and their families and to society in general. About a third of the approximately 40,000 traffic fatalities every year involve drunk drivers, and direct and indirect public health costs are estimated to be in the billions of dollars yearly.

In addition to its enormous toll on families and society at large, alcoholism is devastating to an individual's health because of the damage that excessive amounts of alcohol cause to the system over time. Whether it is the liver or the heart or some other organ, says Koob, "Ultimately, alcoholism gets you as some part of your body goes."

During the next five years, the researchers plan to use molecular, cellular, and physiological methods to identify specific clusters of genes whose expression is regulated by alcohol and to confirm nominated gene targets.

The consortium encourages the integration of diverse studies in the field. For instance, a meta-analysis of knockout-mouse studies examined more than 4.5 million data points on more than 100 microarrays, identifying some 3,800 unique genes and 1,300 functional groups that may determine a predisposition for a high degree of alcohol intake.

"The meta-analysis simply would not have happened without the consortium," Koob says. "The consortium as a whole is greater than its individual components." In addition to Scripps Research and the University of Texas, the consortium's primary sites are: Oregon Health and Science University in Portland; Stanford University and SRI International in Stanford, California; Indiana University Medical Center in Indianapolis; and University of Colorado Health Sciences Center in Denver. Also at Scripps Research are the NIAAA-funded Scripps Research Institute Alcohol Research Center, which focuses on neurobiology of alcohol dependence, and the Pearson Center for Alcoholism and Addiction Research, which is devoted to medication development.

Koob recently published an ambitious and thought-provoking new book, "Neurobiology of Addiction," that emphasizes how rapidly the neurobiology of addiction has emerged and grown as a research field. Some 30 years ago, we knew almost nothing about the neurobiological mechanisms of addiction. Koob has made major contributions to the field.

"There were a couple of surprises in putting the book together," says Koob. "One was how little is known about addiction, as opposed to what drugs do to you initially. It became clear that the field needs to move to a study of dependence - the compulsive use of drugs - from whether or not they make you high."

"Overall, there's still a huge gap in our understanding of how molecular changes translate into cellular changes, which translate into circuitry changes. We're just starting to move away from the idea that these chemicals are floating around in our brain in pools of varying levels. Clearly, interactions are occurring in very specific areas at very specific times. How molecular changes occur to make one person more vulnerable to addiction than another is really the key to the addiction process."

"Once we know the circuits and the basis for alcoholism, we can develop new targeted treatments."