Behavioral and molecular analysis of individual variation of ethanol drinking

乙醇饮用个体差异的行为和分子分析

基本信息

批准号：
7619309
负责人：
JENNIFER T WOLSTENHOLME
金额：
$ 0.94万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-10 至 2009-08-24
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7619309
关键词：
Accounting Adult Affect Alcohol abuse Alcohol consumption Alcoholism Animals Anxiety Behavioral Biological Assay Brain C57BL/6 Mouse Complex Development Disease Environmental Risk Factor Ethanol Gene Expression Genes Genetic Genetic Materials Genomics Goals Heavy Drinking Inbred Strain Inbred Strains Mice Individual Individual Differences Laboratories Measurement Measures Microarray Analysis Modeling Molecular Molecular Analysis Molecular Profiling Molecular Target Mus Neurotransmitters Partner in relationship Pathway interactions Population Reporting Rodent Rodent Model Self Administration Self-Administered Signal Pathway Signal Transduction System Time Training United States Variant alcohol abuse pharmacotherapy alcohol effect design drinking drinking behavior experience new therapeutic target non-genetic preference research study social social stress stressor

项目摘要

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.

描述（由申请人提供）：酒精中毒是一种复杂的多基因疾病，影响了大脑中许多神经递质途径。许多人喝酒，但相对较少的人会产生过度喝酒的趋势。遗传和环境因素都导致了酗酒的发展。据估计，遗传学造成了大约一半过度饮酒的脆弱性。在我们的实验室和其他人中的研究发现，乙醇自我给药模型中的持续性变异性。在实验室模型中，乙醇摄入和偏爱的这些差异可能会受到社会压力的影响，因为与其侵略性，主导的同类产品相比，下属或失败的动物增加了其乙醇的消耗。几乎在遗传上相同的小鼠的近交菌株也显示了饮酒行为的这种个体变异。我们的实验使用近交小鼠菌株“夹住”遗传因素，使我们能够研究社会压力对乙醇饮用行为的个体变异的影响。我们的假设是，社会压力会导致影响乙醇饮用的大脑的持久信号变化。拟议的研究采用了两管齐的方法，行为（两瓶选择饮酒，社会压力和焦虑量测量）和分子（DMA微阵列）测定法，以识别影响乙醇饮用行为的基因网络。实验将利用受试者设计内部和之间的设计。这些实验的目标是：1）表征小鼠的社会压力模型； 2）确定社会压力和焦虑对乙醇饮用的影响； 3）确定涉及饮酒的个体变化以及社会压力对饮酒行为变化的影响的基因网络。使用拟议的模型调查过量饮酒涉及的非遗传因素，我们可能会确定用于治疗酒精滥用和酒精中毒的新型治疗靶标。