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

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

展开

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.

酒精中毒是一个严重的公共卫生问题，对个人和更大的人来说是普遍的成本社区。在美国，有13名成年人是酒精依赖或与酒精有关的问题。一个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 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”。该项目研究了通过将母亲饲养的母亲与幼儿园饲养的恒河猴进行比较，童年应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。通过此应用程序，我们要求额外的资金，以显着扩大我们的能够研究这个独特的实验人群。这里提出的实验将研究如何童年时期的压力和酒精，无论是单独且彼此结合的，在功能上都会改变5-羟色胺突触传递和受体功能的调节。这将使数据添加到第一笔赠款支持的解剖学研究。拟议的研究还将检查谷氨酸和GABAA受体，也称赞第一笔赠款。这些实验代表一个时间的科学机会来产生有关5-羟色胺的功能数据，这些数据无法在其他地方收集。他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绘制的系统，这将是关键的首次系统研究幼儿园猴子大脑中的神经递质系统。该建议也使我们走向跨学科科学的模型，不仅有望提高效率，而且有望获得更丰富的机会单个动物中许多分析层面的数据集成。与公共卫生的相关性：在童年时期经历创伤事件的成年人，例如与他们的父母有滥用酒精和酗酒的风险。这种增加风险的原因是未知。拟议的研究旨在直接解决童年压力的机制通过研究动物的饮酒行为和大脑结构和功能来导致成人酒精中毒经历了孕产妇分离。来自该项目的信息可能会对如何产生重要的影响受创伤的儿童可能受到后来的滥用侵害。