MRS Interrogation of Alcohol's Neurobiochemical Effects

MRS 探究酒精的神经生化效应

基本信息

批准号：
7739634
负责人：
JAMES B DAUNAIS
金额：
$ 7.4万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-10 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7739634
关键词：
Abstinence Address Adult Affect Age Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Animals Anxiety Behavioral Biochemical Biochemistry Blood flow Brain Brain Chemistry Brain region Cercopithecus tantalus Cerebellum Cerebrovascular Circulation Cerebrum Chemical Shift Imaging Choline Chronic Clinic Clinical Communities Control Animal Coupled Data Development Diagnosis Disease Drug Metabolic Detoxication Ethanol Exhibits Exposure to Funding Goals Human Hydrocortisone Image Individual Intervention Lead Light Magnetic Resonance Spectroscopy Malnutrition Measures Medical Monitor Monkeys Neurobiology Neurosciences Nutritional Perfusion Population Positioning Attribute Procedures Public Health Recording of previous events Resolution Rodent Rodent Model Scanning Self Administration Self-Administered Spectrum Analysis Stress Structure Time United States Vitamin Deficiency Withdrawal Work alcohol effect alcohol exposure alcohol response base cost frontal lobe insight magnetic resonance spectroscopic imaging meetings multidrug abuse neurochemistry neuroimaging public health relevance response treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Alcohol abuse continues to be a major problem in the United States with an estimated 14 million adults meeting the clinical criteria for a diagnosis of alcohol abuse or alcoholism at an estimated cost of $185 billion. Chronic alcohol exposure has been shown to impact structure and function of the brain but it is unclear when these effects occur since most of what is known of alcohol's effects on the brain is based on studies of individuals who have abused for a long time and the results can be complicated by many factors incuding polydrug abuse, poor nutritional states and other medical conditions. Another complicating factor is the interaction of stress and alcohol. Using magnetic resonance spectroscopic imaging (MRS), we will examine the effects of chronic alcohol self-administration on brain biochemistry in a group of monkeys that have been selected based on their levels of anxiety/cortisol response to novelty. MRS scans will be acquired to determine whether there are differences in the biochemical state of the brains as a function of anxiety state and then as a result of alcohol exposure. We will conduct MRS measures in the ethanol naive state and again following self-administration. We will also track metabolite changes that might occur as a result of normal development or as a result of different cortisol levels in the control animals. We will be in a position to track any changes that occur early in alcohol abuse which is something that cannot be accomplished in human studies. The results will provide some insight into how the brain reacts to stress and alcohol. These data will be collected in the same animals in which high resolution structural scans and cerebral blood flow data will be acquired providing one more crucial piece of data as to how the brain responds to stress and alcohol interactions. We can control all variables associated with alcohol self-administration in these monkeys. They will be monitored both before and after exposure to alcohol, thus, we will be able to monitor the progression of any changes in the biochemical state that directly results from alcohol exposure. These studies will help identify how exposure to long-term alcohol might affect how the brain works. PUBLIC HEALTH RELEVANCE Alcohol (ethanol) abuse and alcoholism are major public health concerns, affecting an estimated 10% of the U.S. population, at an annual cost of over 100 billion dollars. Adequate treatment and intervention strategies continue to elude the medical community in part because the impact of alcoholism on the brain is not clearly understood. The goal of these proposed studies is to better understand how alcohol exerts it effects on brain metabolites with the hope that better insight into alcohol's neurobiological and neurochemical effects will lead to better treatment strategies.

描述（由申请人提供）：酒精滥用仍然是美国的一个主要问题，估计有 1,400 万成年人符合酒精滥用或酒精中毒诊断的临床标准，估计成本为 1,850 亿美元。长期接触酒精已被证明会影响大脑的结构和功能，但尚不清楚这些影响何时发生，因为大多数已知的酒精对大脑的影响都是基于对长期酗酒者的研究和结果多种因素可能导致病情复杂化，包括滥用多种药物、营养状况不佳和其他医疗状况。另一个复杂的因素是压力和酒精的相互作用。我们将使用磁共振波谱成像（MRS）来检查长期自我饮酒对一组猴子大脑生化的影响，这些猴子是根据它们对新奇事物的焦虑/皮质醇反应水平而选择的。将进行 MRS 扫描，以确定大脑的生化状态是否因焦虑状态和酒精暴露而存在差异。我们将在乙醇初始状态下进行 MRS 测量，并在自我给药后再次进行 MRS 测量。我们还将追踪由于正常发育或对照动物皮质醇水平不同而可能发生的代谢变化。我们将能够追踪酒精滥用早期发生的任何变化，这是人类研究无法实现的。研究结果将提供一些关于大脑如何对压力和酒精做出反应的见解。这些数据将在相同的动物中收集，其中将获得高分辨率结构扫描和脑血流数据，从而提供关于大脑如何对压力和酒精相互作用做出反应的更重要的数据。我们可以控制与这些猴子自我饮酒相关的所有变量。在接触酒精之前和之后都会对它们进行监测，因此，我们将能够监测因酒精接触直接导致的生化状态的任何变化的进展。这些研究将有助于确定长期饮酒可能如何影响大脑的工作方式。公共卫生相关性酒精（乙醇）滥用和酗酒是主要的公共卫生问题，影响着大约 10% 的美国人口，每年造成的损失超过 1000 亿美元。医学界仍然未能找到适当的治疗和干预策略，部分原因是酗酒对大脑的影响尚不清楚。这些拟议研究的目的是更好地了解酒精如何对大脑代谢物产生影响，希望更好地了解酒精的神经生物学和神经化学效应将导致更好的治疗策略。