Early Stress & Alcoholism: Functional Analyses in Brain

早期压力

• 批准号: 7291023
• 负责人: David P Friedman
• 金额: $ 38.2万
• 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/7291023
• 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; 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; mRNA Expression; 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

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）：酗酒是一个严重的公共卫生问题，对个人和更大的社区造成广泛的成本。在美国，每13个成年人中就有一个是酒精依赖者或有与酒精有关的问题。成人酗酒的一个主要危险因素是童年时期的压力和创伤。2003年，PI开始了一项由NIAAA资助的研究，名为“早期压力和酒精中毒：神经生物学分析”。本计画借由比较母猴与保育室饲养的猕猴，研究童年压力与酒精的互动。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，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种独特的实验人群的能力。这里提出的实验将研究儿童期的压力和酒精，无论是单独或相互结合，功能上改变5-羟色胺调制的突触传递和受体功能。这将为第一笔赠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，这也是对第一笔赠款的补充。这些实验代表了一个一次性的科学机会，可以产生关于血清素的功能数据，这些数据在其他地方无法收集。他们将产生关于重要递质系统分布的基本描述性信息，这些信息在灵长类动物中只被不完全映射，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首次系统研究。这一提议也使我们走向了一种跨学科科学的模式，这种模式不仅有望提高效率，而且还为个体动物的多层次分析提供了更丰富的数据集成机会。与公共卫生的相关性：成年人在童年时期经历过与父母分离等创伤性事件，他们酗酒和酗酒的风险增加。这种风险增加的原因尚不清楚。拟议的研究旨在通过研究经历过母亲分离的动物的饮酒行为和大脑结构和功能，直接解决童年压力导致成年酗酒的机制。这个项目的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。