Early Stress & Alcoholism: Functional Analyses in Brain

早期压力

• 批准号: 7049829
• 负责人: David P Friedman
• 金额: $ 39.19万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049829
• 关键词: AMPA receptors; GABA receptor; Macaca mulatta; NMDA receptors; alcoholic beverage consumption; alcoholism /alcohol abuse; amygdala; autoradiography; behavioral /social science research tag; calcium channel; early experience; electrodes; frontal lobe /cortex; gene expression; glutamates; hippocampus; messenger RNA; neurochemistry; neuroregulation; neurotransmitter transport; protein localization; protein structure function; psychological stressor; psychosocial separation; serotonin receptor; tissue /cell culture; voltage gated channel

DESCRIPTION (provided by applicant): Alcoholism is a serious public health problem with widespread costs to individuals and to the larger community. One in 13 adults in the United States is alcohol dependent or has alcohol-related problems. A major risk factor for adult alcoholism is stress and trauma during childhood. In 2003, the PI began an NIAAA-funded study entitled, Early Stress & Alcoholism: Neurobiological Analysis. This project studies the interaction of childhood stress and ethanol by comparing mother-reared to nursery-reared rhesus monkeys. It will study: 1) drinking behavior, 2) endocrine status, 3) the serotonin transporter and receptors, and 4) gene expression. With this application we are requesting additional funding to expand significantly our ability to study this unique experimental population. The experiments proposed here will examine how childhood stress and alcohol, both alone and in combination with each other, functionally alter serotonin modulation of synaptic transmission and receptor-function. This will add data complimentary to the anatomical studies supported by the first grant. The proposed studies will also examine alterations in glutamate and GABAA receptors, also complimenting the first grant. These experiments represent a one- time scientific opportunity to produce functional data about serotonin that cannot be gathered elsewhere. They will generate fundamental descriptive information about the distribution of important transmitter systems that have only been incompletely mapped in primates, and will be the first systematic study of key neurotransmitter systems in the brains of nursery-reared monkeys. This proposal also moves us towards a model of interdisciplinary science that promises not only increased efficiency, but also richer opportunities for data integration across many levels of analysis in individual animals. Relevance to Public Health: Adults, who in childhood, experience traumatic events like separation from their parents, are at increased risk for alcohol abuse and alcoholism. The causes for this increased risk are unknown. The proposed studies are designed to directly address the mechanisms by which childhood stress leads to adult alcoholism by studying the drinking behavior and brain structure and function of animals that experienced maternal separation. This information from this project can have important influences on how traumatized children may be protected from later substance abuse.

描述（由申请人提供）：酗酒是一个严重的公共卫生问题，给个人和更大的社区带来广泛的损失。在美国，三分之一的成年人有酒精依赖或存在与酒精相关的问题。成人酗酒的一个主要危险因素是童年时期的压力和创伤。 2003 年，PI 开始了一项由 NIAAA 资助的研究，题为“早期压力与酒精中毒：神经生物学分析”。该项目通过比较母亲饲养的恒河猴和托儿所饲养的恒河猴，研究童年压力和乙醇的相互作用。它将研究：1) 饮酒行为，2) 内分泌状态，3) 血清素转运蛋白和受体，以及 4) 基因表达。通过此申请，我们请求额外的资金，以显着扩大我们研究这一独特实验群体的能力。这里提出的实验将研究童年压力和酒精，无论是单独还是相互结合，如何在功能上改变突触传递和受体功能的血清素调节。这将为第一笔资助支持的解剖学研究添加补充数据。拟议的研究还将检查谷氨酸和 GABAA 受体的变化，这也是对第一笔资助的补充。这些实验提供了一个一次性的科学机会，可以产生其他地方无法收集的血清素功能数据。他们将生成有关重要神经递质系统分布的基本描述性信息，这些信息在灵长类动物中尚未完全绘制出来，并且将是对保育猴大脑中关键神经递质系统的首次系统研究。该提案还推动我们走向跨学科科学模型，该模型不仅有望提高效率，而且还为单个动物的多个分析层面的数据集成提供了更丰富的机会。与公共卫生的相关性：在童年时期经历过与父母分离等创伤事件的成年人，酗酒和酗酒的风险会增加。这种风险增加的原因尚不清楚。拟议的研究旨在通过研究经历母性分离的动物的饮酒行为以及大脑结构和功能，直接解决童年压力导致成年酗酒的机制。该项目的信息对于如何保护受创伤的儿童免遭药物滥用产生重要影响。