ETHANOL TOLERANCE: IN VIVO SPECTROSCOPY AND DRINKING IN MONKEYS

乙醇耐受性：猴子体内光谱学和饮酒

• 批准号: 8357788
• 负责人: Christopher D Kroenke
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357788
• 关键词: Acute; Affinity; Binding; Binding Sites; Brain; Collection; Data; Development; Ethanol; Funding; Grant; Human; Individual; Intravenous; Investigation; Magnetic Resonance Spectroscopy; Measurement; Measures; Modeling; Monkeys; National Center for Research Resources; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Self Administration; Self-Administered; Series; Signal Transduction; Source; Spectrum Analysis; Testing; United States National Institutes of Health; alcohol effect; behavior measurement; cost; drinking; endophenotype; in vivo; nonhuman primate; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall objective of the proposed studies is to establish ethanol magnetic resonance spectroscopy (MRS) as a translational measure of tolerance. In a series of in vivo MRS experiments following intravenous ethanol administration, we have observed that the size of the ethanol MRS signal is a non-linear function of ethanol concentration. We have developed a framework to interpret this finding in terms of the concentration and affinity of a saturable ethanol binding site (or collection of binding sites) within the brain. Our data corroborate early spectroscopic results from human investigations, and provide an opportunity to extend these earlier findings by incorporating modern analysis strategies and a previously unrecognized biophysical model of ethanol binding interactions with macromolecular constituents. Within this context, we will provide the first direct comparison between ethanol MRS measures of tolerance, well-established behavioral measurements of acute tolerance, and the development of acquired tolerance. Each of these measurements is interpreted in terms of the propensity to self-administer excessive quantities of ethanol, which will also be directly measured in our non-human primate study. First, we are testing the hypothesis that a high degree of innate tolerance to the intoxicating effects of ethanol is detectable through an endophenotype of increased BEC-corrected ethanol MRS signal intensity. Second, we are testing the hypothesis that BEC-corrected ethanol MRS signal intensity increases as an individual transitions from an ethanol-na¿ve state to a state of excessive ethanol self-administration.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 拟定研究的总体目标是将乙醇磁共振波谱（MRS）确定为耐受性的平移测量。 在静脉注射乙醇后的一系列体内MRS实验中，我们观察到乙醇MRS信号的大小是乙醇浓度的非线性函数。我们已经开发了一个框架来解释这一发现的浓度和亲和力的饱和乙醇结合位点（或结合位点的集合）在大脑内。 我们的数据证实了早期的光谱结果，从人类的调查，并提供了一个机会，扩展这些早期的研究结果，将现代分析策略和以前未被识别的生物物理模型的乙醇结合与大分子成分的相互作用。 在这种情况下，我们将提供第一次直接比较乙醇MRS措施的耐受性，建立良好的行为测量急性耐受性，和获得性耐受性的发展。 这些测量值中的每一个都是根据自我给予过量乙醇的倾向来解释的，这也将在我们的非人灵长类动物研究中直接测量。 首先，我们正在测试的假设，即高度的先天性耐受性的酒精中毒的影响是通过增加的BEC校正乙醇MRS信号强度的内表型检测。 第二，我们正在测试的假设，即BEC校正乙醇MRS信号强度增加，作为一个人的过渡，从一个乙醇nave状态过度乙醇自我管理的状态。