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，给个人和更大范围的人带来广泛的损失 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 跨个体动物的多个分析水平的数据集成。 与公共卫生的相关性：在童年时期经历过创伤性事件（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。