$38 Million Grant Awarded to Alcohol Research Consortium

By Mika Ono

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has funded a five-year, $38 million grant to support a consortium led by a scientist at The Scripps Research Institute. The multi-institutional group aims to identify the molecular basis of alcoholism, establishing a platform upon which future treatments can be built.

"Most people in this country drink," says George F. Koob, principal investigator of the grant and professor in the Committee on the Neurobiology of Addictive Disorders at Scripps Research, "yet only some become alcoholics. Why? That's the question we're trying to answer."

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 hundreds of billions of dollars yearly.

The grant represents the first competitive renewal for the consortium, named the Integrative Neuroscience Initiative on Alcoholism, which is made up of 26 lead investigators (including seven core directors) and their teams. The group received its initial round of funding in 2001.

To date, the consortium has made significant scientific progress. Accomplishments include:

• Establishing rodent models of excessive drinking, both for binging and for dependence;
  
  
• Identifying specific genes involved in excessive drinking. While some of these genes are the focus of current investigations (for example, those in the protein kinase pathway), others had never before been implicated in problem drinking (for example, sodium channel genes and a glutamate receptor gene Homer);
  
  
• Recognizing specific brain regions critical to excessive drinking. These include the nucleus accumbens (the one of the brain's so-called "reward centers") and two areas involved in emotional processing—the amygdala and the septal area.

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 group also aims to attract new and innovative investigators to the field of alcohol research.

The consortium both maintains the independence of individual research teams and develops shared resources that would be beyond the reach of any single lab. While lead investigators' projects are funded individually, the consortium provides administrative oversight (including a web site at http://www.scripps.edu/np/inia/) and three shared research areas—focusing on animal models, neurocircuitry, and gene arrays. These common assets facilitate the exchange of technologies, ideas, and expertise.

The consortium also 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 (Proceedings of the National Academy of Sciences, April 17, 2006).

"The meta-analysis simply would not have happened without the consortium," Koob says. "The consortium as a whole is greater than its individual components."

Of the total grant, Scripps Research will receive approximately $7.5 million over five years, funding projects in the laboratories of Koob, Professor George Siggins, and Assistant Professor Amanda Roberts.

The consortium's scientific co-director is Adron Harris of the Waggoner Center for Alcohol and Addiction Research at the University of Texas, Austin. 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.

Another, separate consortium with the name Integrative Neuroscience Initiative on Alcoholism is located in the Eastern states and focuses on characterizing the effects of stress and alcohol on the nervous system.

The NIAAA is one of the 18 institutes that comprise the National Institutes of Health. It supports and conducts biomedical and behavioral research on the causes, consequences, treatment, and prevention of alcoholism and alcohol-related problems. See http://www.niaaa.nih.gov/.

Also at Scripps Research are the NIAAA-funded Scripps Research Institute Alcohol Research Center, which focuses on the neurobiology of alcohol dependence, and the Pearson Center for Alcoholism and Addiction Research, which is devoted to medication development.

Send comments to: mikaono[at]scripps.edu

"Most people in this country drink, yet only some become alchoholics. Why? That's the question we're trying to answer."

—George F. Koob