MRS Interrogation of Alcohol's Neurobiochemical Effects

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1400万成年人符合酒精滥用或酒精中毒的临床诊断标准，估计成本为1850亿美元。长期接触酒精已被证明会影响大脑的结构和功能，但这些影响何时发生尚不清楚，因为已知的酒精对大脑影响的大部分是基于对长期滥用酒精的个人的研究，结果可能会因多种因素而复杂化，包括滥用多种药物、营养不良和其他医疗条件。另一个复杂的因素是压力和酒精的相互作用。利用磁共振波谱成像(MRS)，我们将检测慢性酒精自我管理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/皮质醇反应水平而被挑选出来的。将进行MRS扫描，以确定大脑的生化状态是否因焦虑状态而发生变化，然后是酒精暴露的结果。我们将在乙醇幼稚状态下进行MRS措施，并在自我给药后再次进行。我们还将跟踪由于正常发育或对照组动物皮质醇水平不同而可能发生的代谢物变化。我们将能够跟踪酒精滥用早期发生的任何变化，这是人类研究无法完成的。这一结果将为我们了解大脑对压力和酒精的反应提供一些信息。这些数据将在同一批动物中收集，在这些动物中，将获得高分辨率的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另一个关键数据。我们可以控制这些猴子体内与酒精自我给药相关的所有变量。他们将在酒精暴露之前和之后被监测，因此，我们将能够监测酒精暴露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会如何影响大脑的工作方式。与公共健康相关的酒精滥用和酗酒是主要的公共健康问题，估计影响到10%的美国人口，每年造成的损失超过1000亿美元。医学界仍然没有足够的治疗和干预策略，部分原因是酒精中毒对大脑的影响还没有被清楚地了解。这些拟议研究的目标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影响将导致更好的治疗策略。

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.