Neural Basis of Ethanol Sensitization/Drinking in Mice

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DESCRIPTION (provided by applicant): Alcoholism is caused by a complex interaction of environmental, genetic, and physiological factors. A family history of alcoholism is a strong predictor of high alcohol seeking behavior in humans and in animal models of alcoholism, and the prognosis is worse when an individual has a both high genetic load for alcoholism and a personal history of alcohol use. This proposal seeks a better understanding of neural mechanisms that are altered by alcohol experience. The populations of mice that will be used in this project already show evidence of a link between behavioral sensitization to alcohol's locomotor stimulating effects and alcohol drinking. Specifically, these selectively bred, High Alcohol Preferring (HAP) mice are more likely to show locomotor sensitization (LMS) to ethanol following repeated administration than Low Alcohol Preferring (LAP) mice, indicating that LMS and drinking are likely to be genetically and physiologically linked. Investigating mechanisms underlying LMS may yield insight into the mechanisms of high alcohol drinking. This proposal directly seeks evidence about neural pathways involved in LMS and its relationship to excessive drinking by studying immediate early gene expression. Experiments will also assess whether exposure to alcohol sufficient to induce LMS increases either the incentive value of alcohol and/or alcohol drinking. Finally, because enduring LMS in HAP mice requires that they associate their test environment with previous alcohol injections, studies will seek to understand whether the memory of alcohol affects alcohol drinking and the incentive value of alcohol. One study will also test whether acamprosate, a treatment for alcoholism, can reverse changes in the rewarding value of alcohol caused by alcohol exposure. The hypothesis is that associative forms of neural and behavioral plasticity underlie both the acquisition of excessive drinking and LMS, and that the amygdala may lie at the heart of this interaction.