Early Stress & Alcoholism: Functional Analyses in Brain

早期压力

基本信息

批准号：
7493048
负责人：
David P Friedman
金额：
$ 43.84万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
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/7493048
关键词：
AMPA Receptors Address Adult Affect Agonist Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Amygdaloid structure Animals Area Autoradiography Behavioral Brain Brain region Childhood Chromosome Pairing Chronic stress Classification Communities Complex Coupling Cytoplasmic Granules Data Development Endocrine Ethanol Event Exhibits Funding Gene Expression Glutamates Grant Heavy Drinking High voltage activated calcium channel Hippocampal Formation Hippocampus (Brain)Hypothalamic structure In Vitro Individual Lateral Lead Life Long-Term Effects Macaca mulatta Maps Measures Medial Mediating Messenger RNA Modeling Monkeys Mothers N-Methyl-D-Aspartate Receptors N-Methylaspartate Neurobiology Neurons Neurotransmitters Nurseries Outcome Parents Physiological Population Prefrontal Cortex Primates Procedures Prosencephalon Public Health Receptor Gene Recording of previous events Relative (related person)Request for Applications Research Research Design Research Personnel Residual state Risk Risk Factors Science Self Administration Serotonin Serotonin Receptor 5-HT1A Slice Standards of Weights and Measures Stress Structure Substance abuse problem Synapses Synaptic Receptors Synaptic Transmission System Techniques Testing Time Trauma United States alcohol and other drug alcohol effect alcohol related problem alcohol response alcoholism/alcohol abuse alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid amino 3 hydroxy 5 methylisoxazole 4 propionate cost data integration density dentate gyrus design drinking drinking behavior drug of abuse early childhood experience gamma-Aminobutyric Acid maternal separation neurochemistry neurotransmission patch clamp postsynaptic presynaptic programs raphe nuclei receptor receptor function research study response serotonin receptor serotonin transporter transmission process traumatized children

项目摘要

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.

酗酒是一个严重的公共卫生问题，给个人和更大范围的人造成广泛的损失社区。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。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 NIAAA 资助的研究题为“早期压力与酒精中毒：神经生物学分析”。该项目研究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) 血清素转运体和受体，以及 4）基因表达。通过此申请，我们请求额外的资金来大幅扩展我们的业务研究这个独特的实验群体的能力。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，都会在功能上改变血清素突触传递和受体功能的调节。这将补充数据解剖学研究得到第一笔资助的支持。拟议的研究还将检查谷氨酸和 GABAA 受体，也对第一笔资助表示赞赏。这些实验代表了一个—— 时间科学机会产生有关血清素的功能数据，这些数据无法在其他地方收集。它们将生成有关重要发射机分布的基本描述信息该系统仅在灵长类动物中得到不完整的绘制，这将是对关键系统的第一个系统研究保育猴大脑中的神经递质系统。这项建议也促使我们走向跨学科科学模型不仅有望提高效率，而且还可以提供更丰富的机会对个体动物进行多个层次分析的数据集成。与公共卫生的相关性：在童年时期经历过创伤事件（例如与父母分离）的成年人他们的父母酗酒和酗酒的风险增加。造成这种风险增加的原因是未知。拟议的研究旨在直接解决儿童压力的机制通过研究动物的饮酒行为以及大脑结构和功能，导致成人酗酒经历过母子分离。来自该项目的信息可能会对如何产生重要影响受创伤的儿童可能会受到保护，免于日后滥用药物。