BEHAVIORAL GENOMICS OF ALCOHOL NEUROADAPTATION

酒精神经适应的行为基因组学

• 批准号: 8357785
• 负责人: KATHLEEN A GRANT
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357785
• 关键词: Alcohol abuse; Alcohol consumption; Alcohols; Area; Brain; CCL18 gene; Chronic; Ethanol; Funding; Genes; Genetic; Grant; Heavy Drinking; Human; Impulsive Behavior; Impulsivity; Individual; Individual Differences; Macaca fascicularis; Measures; Medial; Modeling; Monkeys; National Center for Research Resources; Population; Prefrontal Cortex; Primates; Principal Investigator; Psychological reinforcement; Recording of previous events; Research; Research Infrastructure; Resources; Risk; Self Administration; Source; Translating; United States National Institutes of Health; Variant; alcohol effect; alcohol exposure; behavioral genomics; chronic alcohol ingestion; cost; functional genomics; human subject; neuroadaptation; nonhuman primate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project aims at understanding individual variation in risk for excessive drinking, with a focus on impulsive behaviors. A history of heavy ethanol intake appears to be related to increases in measures of impulsivity in humans. However human subject studies have been unable to distinguish antecedent baseline measures of impulsivity from the consequential effects of a history of heavy ethanol consumption. Our model of ethanol self-administration in cynomolgus monkeys provides a unique and important model of alcohol abuse, and reflects the individual differences in propensity to drink alcohol noted in the human population. Because of genetic similarities between humans and non-human primates, these studies can then be a key step in translating candidate mechanisms of ethanol's effects into the human condition through functional genomics. Thus, our primary focus of this PARC project is to use the monkey model to characterize antecedent and consequent measures of two aspects of impulsivity (the ability to rapidly stop, or withhold, responding and the aversion to a delay in reinforcement) with genetic factors related to excessive ethanol self-administration. Our Specific Aims are: (1) To determine if measures of impulsivity prior to alcohol exposure will predict chronic alcohol self-administration over a 12 month period; (2) To determine if chronic ethanol self-administration increases measures of impulsivity; and (3) To determine the expression of key gene networks in a brain area related to impulsive behaviors (the orbital medial prefrontal cortex) both prior to and following chronic alcohol drinking.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目旨在了解过度饮酒风险的个体差异，重点是冲动行为。大量乙醇摄入史似乎与人类冲动性指标的增加有关。然而，人类受试者的研究一直无法区分先前的基线测量冲动的后果影响的历史，大量的乙醇消费。 我们在食蟹猴中的乙醇自我给药模型提供了一种独特且重要的酒精滥用模型，并反映了人群中饮酒倾向的个体差异。由于人类和非人类灵长类动物之间的遗传相似性，这些研究可以成为通过功能基因组学将乙醇影响的候选机制转化为人类状况的关键一步。 因此，我们这个PARC项目的主要重点是使用猴子模型来表征冲动性的两个方面（快速停止或抑制反应的能力和对延迟强化的厌恶）的前因和后果措施，这些因素与过度乙醇自我管理有关。 我们的具体目标是：（1）确定酒精暴露前的冲动性指标是否能预测12个月内的长期自我饮酒;（2）确定长期自我饮酒是否会增加冲动性指标;（3）确定长期饮酒前后与冲动行为相关的大脑区域（眶内侧前额叶皮层）中关键基因网络的表达。