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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 拟议的研究的总体目的是建立乙醇磁共振光谱（MRS）作为耐受性的翻译测量。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功能。我们已经开发了一个框架来解释这一发现，以大脑内饱和乙醇结合位点（或结合位点的收集）的浓度和亲和力。我们的数据证实了人类投资的早期光谱结果，并通过纳入现代分析策略和以前未被认可的乙醇结合相互作用与大分子宪法的生物物理模型来扩展这些早期发现。在这种情况下，我们将提供乙醇MRS的耐受性测量，良好的急性公差行为测量以及获得的耐受性的发展之间的首次直接比较。这些测量值中的每一个都是根据自我管理过量数量的乙醇的承诺来解释的，这也将在我们的非人类灵长类动物研究中直接测量。首先，我们正在检验以下假设：通过增加BEC校正的乙醇MRS信号强度的内表型，可以检测到对乙醇醉酒作用的天生耐受性。其次，我们正在检验以下假设：BEC校正的乙醇MRS信号强度随着个体从乙醇的过渡到过度乙醇自我给药状态而增加。