Network Theory Analysis of Ethanol Self Administering Non-Human Primates

非人灵长类动物自我管理乙醇的网络理论分析

• 批准号: 8263785
• 负责人: Qawi Kevin Telesford
• 金额: $ 4.22万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-05 至 2014-04-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8263785
• 关键词: Address; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Aminobutyric Acids; Anatomy; Anesthesia procedures; Animal Model; Animals; Area; Behavioral; Brain; Brain region; CNS processing; Cercopithecus tantalus; Characteristics; Chronic; Chronic Phase; Clinic; Clinical; Complex; Consumption; Data; Disease; Dose; Endocrine; Ethanol; Exhibits; Exposure to; Functional Magnetic Resonance Imaging; Glutamates; Grant; Graph; Healthcare; Heavy Drinking; Hepatic; Human; Individual; Lead; Length; Light; Link; Macaca; Metric; Modeling; Neurobiology; Neurotransmitters; Pattern; Pharmaceutical Preparations; Physiological; Population; Process; Property; Proteomics; Published Comment; Recording of previous events; Reliance; Reporting; Research; Rest; Rodent; Scanning; Science; Self Administration; Self-Administered; Specificity; System; Time; Translating; United States; alcohol exposure; alcohol research; chronic alcohol ingestion; cohort; drinking; economic cost; functional genomics; gamma-Aminobutyric Acid; insight; neuroimaging; nonhuman primate; problem drinker; public health relevance; theories

DESCRIPTION (provided by applicant): As the economic cost of healthcare continues to rise in the United States, the issues related to alcohol abuse and dependence are becoming an increasing problem. Consequently, research addressing and treating alcohol abuse and dependence is instrumental to our understanding of the disease. By understanding the mechanisms that lead to alcohol dependence, medications and treatments can be better tailored to treating the disease. Chronic alcohol abuse is linked to reductions in brain activity, affecting two key neurotransmitters, GABA (-aminobutyric acid) and glutamate. While some of the mechanisms and physiological changes that lead to alcohol dependence are well understood, what is not clear is the time course in which these changes might occur. The time course is not understood partially because of reliance on rodent studies, which do not easily translate to humans due to differences in neurobiology and anatomy. In addition, studies in humans are typically done in clinical populations, which may not generalize to the general alcoholic population, many of whom are asymptomatic and do not seek treatment. Many current findings in alcohol research employ region- specific models to study alcohol. However, the brain is a complex system with multiple interacting components, which makes some findings difficult to interpret. The proposed study will address some of these critical issues found in alcohol research by utilizing functional magnetic resonance imaging (fMRI) to investigate the functional changes in non-human primates that have chronically self-administered ethanol. Using network theory of the brain to analyze our data, we plan to demonstrate that fMRI networks can be used to assess the changes in the brain brought about by alcohol dependence. During this study, we will use our well-validated animal model to help us understand the changes in the networks of vervet monkeys that have chronically self-administered ethanol, which may offer insight into the changes in the human brain that lead to alcohol dependence. PUBLIC HEALTH RELEVANCE: As the economic cost of healthcare continues to rise in the United States, the issues related to alcohol abuse and dependence are becoming an increasing problem. Consequently, research into the mechanisms underlying alcohol abuse and dependence is instrumental to our understanding of the disease. During this study, we will study the brain networks of non-human primates after ethanol induction to evaluate the changes in their whole-brain connectivity due to chronic alcohol exposure.

描述（由申请人提供）：随着美国医疗保健的经济成本在美国继续上升，与酒精滥用和依赖有关的问题正成为一个日益严重的问题。因此，解决和治疗酒精滥用和依赖性的研究对我们对疾病的理解至关重要。通过了解导致酒精依赖的机制，可以更好地量身定制药物和治疗方法。慢性酒精滥用与脑活动的减少有关，影响了两个关键的神经递质，GABA（-Aminobutric Acid）和谷氨酸。尽管对导致酒精依赖性的某些机制和生理变化有充分的了解，但不清楚可能发生这些变化的时间过程。由于依赖啮齿动物的研究，由于神经生物学和解剖学的差异，时间过程没有部分理解。此外，对人类的研究通常是在临床人群中进行的，临床人群可能不会推广到一般酒精饮料，其中许多人无症状，并且不寻求治疗。目前在酒精研究中的许多发现采用特定于区域的模型来研究酒精。但是，大脑是一个复杂的系统，具有多个相互作用的组件，这使得一些发现难以解释。拟议的研究将通过利用功能磁共振成像（fMRI）来研究酒精研究中发现的一些关键问题，以研究具有长期自我管理乙醇的非人类灵长类动物的功能变化。使用大脑网络理论来分析我们的数据，我们计划证明fMRI网络可用于评估酒精依赖性带来的大脑变化。在这项研究中，我们将使用验证良好的动物模型来帮助我们了解具有长期自我管理的乙醇网络的变化，这可能会深入了解导致酒精依赖性的人脑的变化。 公共卫生相关性：随着美国医疗保健的经济成本继续上升，与酒精滥用和依赖有关的问题正成为一个越来越多的问题。因此，对酒精滥用和依赖性的机制的研究对我们对疾病的理解至关重要。在这项研究中，我们将研究乙醇诱导后非人类灵长类动物的大脑网络，以评估由于慢性酒精暴露而导致其全脑连通性的变化。