Brain region gene expression responds discretely to chronic alcohol withdrawal with specific disruption of the hippocampus during intoxication

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Berman, Ari Ethan

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Alcoholism is a chronic, progressive and heritable disease that affects millions of Americans and costs the United States hundreds of billions of dollars per year in medical expenditures, property damage, and loss of productivity. Alcohol dependence is the result of long-lasting cellular and molecular changes in the brain that are initiated and maintained by the repeated ingestion of intoxicating amounts of alcohol. Withdrawal symptoms from alcohol occur when alcohol intake is reduced or halted and the brain enters a period of extended hyperactivity. Animal models for alcohol-related behaviors were previously developed and characterized in both mice and rats, including mouse strains that were particularly sensitive to alcohol withdrawal. Mice from a strain that is highly sensitive to withdrawal from alcohol, DBA/2J, were given a chronic dose of ethanol by inhalation and comparative microarray analysis was performed. A suite of microarray analysis software was written to facilitate the large amount of data collected from this experiment, and a robust web-based database system, the Alcohol Research Integrator, was developed to serve both as a storage and as a high-level analysis medium. Here we show that detectable gene expression changes occur in a discrete fashion between gross anatomical brain regions at various stages of withdrawal, and that the hippocampus shows a markedly greater level of gene expression change during intoxication than any of the other brain regions suggesting a particular vulnerability to the intoxicating effects of alcohol.