NIAAA Steps Up Search for Brain Mechanisms of Alcohol Abuse, Alcoholism

The National Institute on Alcohol Abuse and Alcoholism announces a 5-year initiative funded at approximately $50 million to define the brain circuits and mechanisms that underlie behavioral responses to chronic and excessive alcohol consumption. The multidisciplinary Integrative Neuroscience Initiative on Alcoholism (INIA) will integrate research knowledge from animal and human studies and multiple analytic approaches to understand the behavioral neuroadaptive process �� changes in the brain that occur with chronic alcohol exposure that contribute to excessive drinking.

"Neuroadaptation produces a variety of behavioral responses implicated in the disorders alcohol abuse (a harmful drinking pattern that does not entail addiction) and alcohol dependence or addiction, commonly known as alcoholism," said NIAAA Acting Director Raynard Kington, M.D., Ph.D. "In particular, INIA seeks to clarify the mechanisms of reinforcement, tolerance, and sensitization that drive compulsive drinking, and the withdrawal and relapse that complicate successful treatment. As with all alcohol research, INIA has as its ultimate goal improved treatment and preventive interventions."

Researchers are making rapid progress toward understanding brain responses to chronic drinking. However, much of this work is conducted as independent projects that use different analytic approaches, experimental designs, and animal models. The result is that comparing and integrating accumulated data can be difficult. INIA will complement these independent experimental findings and stimulate progress to understand reinforcement (the rewarding effects of drinking alcohol that evoke repeated use), tolerance (the need for increasing amounts of alcohol to produce a desired effect), sensitization (increased response to alcohol after repeated intermittent exposures), withdrawal (negative symptoms occurring with abrupt discontinuation of chronic alcohol consumption), and relapse (resumption of heavy drinking following a period of abstinence).

The largest ever concerted effort to collect and integrate scientific data on neuroadaptation to alcohol consumption, INIA involves two principal scientific consortia comprising multiple leading research institutions across the United States. Each consortium will pursue three overarching goals: to establish models to identify and study specific neurobiological targets for vulnerability to alcohol intake at the molecular, cellular, and neural circuit levels of analysis; to identify clusters of genes whose expression is regulated by alcohol ingestion and that are specific to a given behavioral model of excessive alcohol consumption; and to attract new and innovative investigators to alcohol research. "INIA is expected to create new resources for understanding alcoholism mechanisms, and to provide opportunities for collaboration between scientists in the alcohol field and prominent investigators from other research areas," said Samir Zakhari, Ph.D., Director, NIAAA Division of Basic Research.

A neuroinformatics core within each consortium will allow all investigators access to genetic, molecular, cellular, anatomic, physiologic, neural network, and behavioral data. INIA also will perform and develop capacity for computational neurobiology research on the functional organization and operation of the brain. "INIA affords its component research groups access to resources, information, technologies, ideas, and expertise far beyond the scope of any single research team," said Antonio Noronha, Ph.D., Chief, Neuroscience and Behavior Branch, who coordinates INIA activities at NIAAA.

The first-funded INIA consortium, led by The Scripps Research Institute (TSRI), San Diego, California (Consortium Coordinator and Principal Investigator: George F. Koob, Ph.D.), will attempt to identify neuroadaptive changes that occur in the amygdala, a brain region that makes up part of the brains reward circuitry. Entitled "The Neurobiological Basis of Excessive Drinking," this consortium will test the hypothesis that genetic differences and other changes in the neurobiological processes within the amygdala are responsible for variation in vulnerability to alcohol consumption. Additional participating sites include The University of Texas-Austin, the Oregon Health Sciences University, Indiana University School of Medicine, The University of Colorado Health Sciences Center, and Stanford University and SRI International.

The second INIA consortium, led by the Wake Forest University School of Medicine (Consortium Coordinator and Principal Investigator: Kathleen Grant, Ph.D.), will use a multidisciplinary approach to identify the neurochemistry and neural circuits involved in alcohol-stress interactions. Entitled "The Stress-Anxiety of Alcohol Abuse," this consortium also brings together scientists from The University of Memphis (Tennessee), the University of Tennessee Health Sciences Center, and Vanderbilt University to explore the idea that excessive drinking is used to relieve anxiety, the role of alcohol in exacerbating stress disequilibrium, the role of alcohol in altering normal responses to stressful stimuli, and genes that affect or are affected by alcohol-stress interactions.

For 2002, NIAAA already has expanded INIA to encourage the use of anatomical (tracer) mapping, multi-unit electrophysiological recording techniques in behaving animals, other state-of-the-art methods to identify neural circuits and pathways involved in the alcohol response, and the use of neurocomputational and theoretical approaches to predict drinking-induced neuroadaptation. Future studies will include clinical research on the neuroadaptive behaviors developed in response to excessive alcohol consumption.

A full description of INIA is contained in RFA-AA-01-002 and RFA AA-02-009 in the NIH Guide at http://www.nih.gov. For additional information, please contact Dr. Noronha at (telephone) 301/443-7722 or (email) [email protected].

The National Institute on Alcohol Abuse and Alcoholism, a component of the National Institutes of Health, U.S. Department of Health and Human Services, conducts and supports approximately 90 percent of U.S. research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to science, practitioner, policy making, and general audiences.