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: 8173271
• 负责人: Christopher D Kroenke
• 金额: $ 7.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173271
• 关键词: Acute; Affinity; Binding; Binding Sites; Brain; Collection; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Ethanol; Funding; Grant; Human; Individual; Institution; Intravenous; Investigation; Magnetic Resonance Spectroscopy; Measurement; Measures; Modeling; Monkeys; Research; Research Personnel; Resources; Self Administration; Self-Administered; Series; Signal Transduction; Source; Spectrum Analysis; Testing; United States National Institutes of Health; alcohol effect; behavior measurement; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 will be 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 will test 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 will test 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 拟议研究的总体目标是建立乙醇磁共振波谱（MRS）作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。我们开发了一个框架，根据大脑内可饱和乙醇结合位点（或结合位点集合）的浓度和亲和力来解释这一发现。 我们的数据证实了人类研究的早期光谱结果，并提供了通过结合现代分析策略和先前未被认识的乙醇与大分子成分结合相互作用的生物物理模型来扩展这些早期发现的机会。 在此背景下，我们将首次对乙醇 MRS 耐受性测量、成熟的急性耐受性行为测量以及获得性耐受性的发展进行直接比较。 这些测量中的每一个都将根据自我施用过量乙醇的倾向来解释，这也将在我们的非人类灵长类动物研究中直接测量。 首先，我们将测试以下假设：通过 BEC 校正的乙醇 MRS 信号强度增加的内表型，可以检测到对乙醇中毒作用的高度先天耐受性。 其次，我们将测试以下假设：随着个体从无乙醇状态转变为过量乙醇自我施用状态，BEC 校正的乙醇 MRS 信号强度会增加。