Early Stress & Alcoholism: Functional Analyses in Brain

描述(申请人提供)：酗酒是一个严重的公共卫生问题，对个人和更大的社区都会造成广泛的损失。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。成人酗酒的一个主要风险因素是童年时期的压力和创伤。2003年，该协会开始了一项由NIAAA资助的研究，题为《早期应激与酒精中毒：神经生物学分析》。这个项目通过比较母亲养育的恒河猴和养育的恒河猴来研究童年压力和酒精的相互作用。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，以显着扩大我们研究这一独特的实验人群的能力。这里提出的实验将研究童年压力和酒精如何单独和相互结合，在功能上改变5-羟色胺对突触传递和受体功能的调节。这将为第一笔拨款支持的解剖学研究增加补充数据。拟议的研究还将检查谷氨酸和GABAA受体的变化，这也是对第一笔拨款的赞扬。这些实验代表着一次性的科学机会，可以产生其他地方无法收集的关于5-羟色胺的功能数据。它们将产生关于重要递质系统分布的基本描述性信息，这些信息只在灵长类动物中被绘制得不完全，并且将是对托儿所饲养的猴子大脑中关键神经递质系统的第一次系统研究。这一提议还推动我们走向一种跨学科科学模型，该模型不仅承诺提高效率，还承诺在单个动物的多个层次的分析中提供更丰富的数据集成机会。与公共卫生相关：成年人在童年经历过与父母分离等创伤事件，酗酒和酗酒的风险增加。这种风险增加的原因尚不清楚。这项拟议的研究旨在通过研究经历母体分离的动物的饮酒行为以及大脑结构和功能，直接探讨童年压力导致成年酒精中毒的机制。来自该项目的这些信息可以对如何保护受创伤的儿童免受后来的药物滥用产生重要影响。

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.