MRS Interrogation of Alcohol's Neurobiochemical Effects

MRS 探究酒精的神经生化效应

• 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
• 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

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）：在美国，酗酒仍然是一个主要问题，估计有1400万成人符合诊断酗酒或酒精中毒的临床标准，估计成本为1.85亿美元。慢性酒精暴露已被证明会影响大脑的结构和功能，但尚不清楚这些影响何时发生，因为大多数对酒精对大脑的影响的大多数是基于对长期滥用的个体的研究，而不断滥用Polydrug的许多因素可能会使结果复杂化，而滥用多药，营养状况不佳和其他医疗状况。另一个复杂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给药对脑生物化学在一组猴子中的影响，这些猴子是根据其对新颖性的焦虑/皮质醇反应水平选择的。将获得扫描太太，以确定大脑的生化状态与焦虑状态的关系以及由于酒精暴露的结果是否存在差异。我们将在乙醇幼稚状态下进行MRS措施，并在自我管理之后再次进行。我们还将跟踪由于正常发育或对照动物中皮质醇水平不同而导致的代谢物变化。我们将有能力跟踪酗酒早期发生的任何变化，这是人类研究无法完成的事情。结果将为大脑对压力和酒精的反应提供一些洞察力。这些数据将集中在相同的动物中，在同一动物中，将获得高分辨率结构性扫描和脑血流数据，从而为大脑对压力和酒精相互作用的反应提供了更多关键数据。我们可以控制这些猴子中与酒精自给自足相关的所有变量。他们将在暴露于酒精之前和之后对它们进行监测，因此，我们将能够监测直接因酒精暴露而导致的生化状态变化的进展。这些研究将有助于确定长期酒精的接触如何影响大脑的运作方式。公共卫生相关性酒精（乙醇）滥用和酒精中毒是主要的公共卫生问题，估计影响美国人口的10％，年龄超过1000亿美元。充分的治疗和干预策略继续躲避医学界，部分原因是酒精中毒对大脑的影响尚不清楚。这些拟议的研究的目的是更好地了解酒精如何对脑代谢产生影响，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。