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）：酒精中毒是一个严重的公共卫生问题，对个人和更大的社区的成本普及。在美国，有13名成年人是酒精依赖或与酒精有关的问题。成人酒精中毒的主要危险因素是儿童时期的压力和创伤。 2003年，PI开始了一项由NIAAA资助的研究，标题为“早期压力和酒精中毒：神经生物学分析”。该项目通过将母亲饲养的母亲与育苗的恒河猴进行比较，研究了儿童期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）5-羟色胺转运蛋白和受体，以及4）基因表达。通过此应用，我们要求额外的资金，以大大扩展我们研究这种独特的实验人群的能力。这里提出的实验将研究儿童期压力和酒精如何单独且相互结合，在功能上会改变突触传播和受体功能的5-羟色胺调节。这将为第一笔赠款支持的解剖学研究提供免费的数据。拟议的研究还将检查谷氨酸和GABAA受体的变化，也称赞第一个赠款。这些实验代表了一次一次科学机会，以产生有关5-羟色胺的功能数据，而这些功能数据无法在其他地方收集。他们将生成有关仅在灵长类动物中未完全映射的重要发射器系统的分布的基本描述性信息，并且将成为托儿所的猴子大脑中关键神经递质系统的首次系统研究。该建议还使我们迈向了跨学科科学模型，该模型不仅有望提高效率，而且还有望在单个动物中许多分析的数据集成机会。与公共卫生相关的是：在童年时期，成年人经历了创伤事件，例如与父母分离，他们的酗酒和酒精中毒风险增加。这种增加风险的原因尚不清楚。拟议的研究旨在直接解决儿童期压力通过研究饮酒行为，大脑结构以及经历过母体分离的动物的功能而导致成人酒精中毒的机制。该项目的这些信息可能会对如何保护受创伤的儿童免受后来的滥用。