Early Stress & Alcoholism: Functional Analyses in Brain

酗酒是一个严重的公共卫生问题，对个人和更大的人都会造成广泛的损失。 社区。在美国，每13个成年人中就有一个依赖酒精或有与酒精相关的问题。一个 成人酗酒的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 NIAAA资助的题为《早期压力和酒精中毒：神经生物学分析》的研究。本项目研究的是 通过比较母亲养育的恒河猴和养育的恒河猴，童年压力和酒精的交互作用。 它将研究：1)饮酒行为，2)内分泌状态，3)5-羟色胺转运体和受体，以及 4)基因表达。通过这项申请，我们正在申请额外的资金，以显著扩大我们的 研究这一独特的实验种群的能力。这里提出的实验将检验如何 童年压力和酒精，无论是单独还是相互结合，都会在功能上改变5-羟色胺 突触传递和受体功能的调节。这将为数据添加补充 第一笔拨款资助的解剖学研究。拟议的研究还将检查在 谷氨酸和GABAA受体，也是对第一笔赠款的赞扬。这些实验代表了一个-- 时间，科学机会，以产生有关5-羟色胺的功能数据，这是在其他地方无法收集的。 它们将生成有关重要发射器分布的基本描述性信息 仅在灵长类动物中尚未完全绘制的系统，将是第一次系统地研究 育儿猴大脑中的神经递质系统。这项提议还将使我们走向 跨学科科学的模式，不仅承诺提高效率，而且提供更丰富的 在单个动物中跨多个层次的分析进行数据集成。 与公共卫生的相关性：在童年经历过创伤事件的成年人，比如与 他们的父母酗酒和酗酒的风险增加。这种风险增加的原因是 未知。这项拟议的研究旨在直接解决儿童压力的机制 通过研究饮酒行为以及动物的大脑结构和功能来导致成年酒精中毒 经历了母性分离。来自该项目的信息可以对以下方面产生重要影响 受到创伤的儿童可能会得到保护，不会在以后滥用药物。

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.