Early Stress & Alcoholism: Functional Analyses in Brain

早期压力

• 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
• 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

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，对个人和更大的群体都有广泛的成本。 社区在美国，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。一 成年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资助的研究，题为早期压力和酒精中毒：神经生物学分析。该项目研究了 通过比较母亲饲养的恒河猴和托儿所饲养的恒河猴来研究儿童期压力和乙醇的相互作用。 它将研究：1）饮酒行为，2）内分泌状况，3）血清素转运体和受体， 4)基因表达。通过这项申请，我们要求额外的资金，以显着扩大我们的 研究这个独特的实验群体的能力。这里提出的实验将研究如何 儿童时期的压力和酒精，无论是单独还是相互结合，都会在功能上改变血清素 调节突触传递和受体功能。这将向 第一笔赠款支持的解剖学研究。拟议的研究还将审查 谷氨酸和GABAA受体，也是第一笔赠款的补充。这些实验代表了一个- 时间科学的机会，产生功能数据的血清素，不能在其他地方收集。 它们将产生关于重要发射器分布的基本描述信息 系统，只有不完全映射在灵长类动物，并将是第一个系统的研究关键 在托儿所饲养的猴子的大脑中的神经递质系统。这一建议也使我们走向一个 跨学科科学的模式，不仅承诺提高效率，而且还提供更丰富的机会， 在个体动物的多个分析水平上进行数据集成。 与公共卫生的相关性：在童年时期经历创伤性事件（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。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、大脑结构和功能， 经历了母亲的分离。这个项目的信息可以对如何 受创伤的儿童可能受到保护，以后不会滥用药物。