Behavioral and molecular analysis of individual variation of ethanol drinking

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DESCRIPTION (provided by applicant): Alcoholism is a complex, polygenic disease affecting many neurotransmitter pathways in the brain. Many people drink alcohol, but relatively few develop the tendency to drink excessively. Both genetic and environmental factors contribute to this development of alcohol abuse. It has been estimated that genetics contributes to about half of the vulnerability to drink excessively. Studies in our laboratory and others have found persistent individual variability in rodent models of ethanol self-administration. These differences in ethanol intake and preference, in a laboratory model, may be affected by social stress since subordinate or defeated animals increase their ethanol consumption as compared to their aggressive, dominant counterparts. Inbred strains of mice, which are virtually genetically identical, have also shown such individual variation in drinking behaviors. Our experiments use an inbred mouse strain to "clamp" the genetic factors allowing us to study the effects of social stress on the individual variation of ethanol drinking behavior. It is our hypothesis that social stress causes long-lasting signaling changes in the brain that influence ethanol drinking. The proposed study uses a two-pronged approach, behavioral (two-bottle choice drinking, social stress and anxiety measurements) and molecular (DMA microarrays) assays to identify the gene networks affecting ethanol drinking behavior. Experiments will utilize a within and between subjects design. The goals of these experiments are: 1) to characterize a model of social stress in mice; 2) to identify the effects of social stress and anxiety on ethanol drinking; and 3) to identify the gene networks involved in both individual variation of drinking and the effects of social stress on the variation of drinking behavior. Using the proposed model to investigate the non-genetic factors involved in excessive alcohol drinking, we may identify novel therapeutic targets for treating alcohol abuse and alcoholism.