MRS Interrogation of Alcohol's Neurobiochemical Effects

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，估计费用为1850亿美元。慢性酒精暴露已被证明会影响大脑的结构和功能，但目前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是基于对长期滥用的个体的研究，结果可能会因多种药物滥用，营养状况差和其他医疗条件等因素而复杂化。另一个复杂的因素是压力和酒精的相互作用。使用磁共振光谱成像（MRS），我们将研究慢性酒精自我管理对大脑生化的影响，在一组猴子中，这些猴子是根据他们对新奇事物的焦虑/皮质醇反应水平选择的。将获得MRS扫描，以确定大脑的生化状态是否存在差异，作为焦虑状态的函数，然后作为酒精暴露的结果。我们将在未使用乙醇的状态下进行MRS测量，并在自我给药后再次进行MRS测量。我们还将跟踪可能由于正常发育或对照动物中不同皮质醇水平而发生的代谢物变化。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。研究结果将有助于了解大脑对压力和酒精的反应。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，提供关于大脑如何响应压力和酒精相互作用的另一个关键数据。我们可以控制所有与这些猴子自我饮酒相关的变量。他们将在接触酒精之前和之后进行监测，因此，我们将能够监测由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接触酒精如何影响大脑的工作。酒精（乙醇）滥用和酒精中毒是主要的公共卫生问题，影响了估计10%的美国人口，每年花费超过1000亿美元。适当的治疗和干预策略仍然远离医学界，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作用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.