Optical probe for continuous real-time in vivo study of brain alcohol

用于连续实时体内脑酒精研究的光学探针

• 批准号: 10527743
• 负责人: Tanya Hutter
• 金额: $ 20.65万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-18 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527743
• 关键词: Acetates; Affect; Alcohol consumption; Alcohols; Algorithms; Animal Model; Animals; Area; Behavior; Behavioral; Blood; Brain; Caliber; Calibration; Concentration measurement; Consumption; Dependence; Detection; Development; Diagnostic; Dimensions; Dose; Drug Kinetics; Ethanol; Fiber; Forensic Medicine; Gas Chromatography; Geometry; Goals; Individual; Intervention; Liquid substance; Measurement; Measures; Medical; Membrane; Microdialysis; Modeling; Monitor; Motivation; Nature; Neurobiology; Optics; Perfusion; Pharmacology; Pharmacotherapy; Phase; Physiological; Physiological Processes; Prevention; Public Health; Public Policy; Rattus; Reading; Rodent; Sampling; Self Administration; Techniques; Technology; Temperature; Testing; Time; Tissues; Training; United States; Water; alcohol effect; alcohol exposure; alcohol measurement; alcohol research; alcohol use disorder; brain tissue; design; detection limit; drinking; experimental study; improved; in vivo; in vivo evaluation; infrared spectroscopy; interstitial; neurobiological mechanism; neurochemistry; neurophysiology; novel therapeutics; optical fiber; performance tests; small molecule; surface coating; technology development; temporal measurement; transmission process; vapor

PROJECT ABSTRACT Development of new therapeutics for alcohol use disorder requires continued progress in the elucidation of the neuropharmacological mechanisms that underlie the changes in the brain that repeated ethanol consumption produce. To this end, animal models, including rodents, have been essential in furthering our understanding of how ethanol exposure alters the motivation to consume ethanol. A key limitation in the field is the ability to monitor ethanol in tissues (including brain) in real-time so that the experimenter can interpret any findings of neurophysiological or neurochemical changes produced by ethanol. In other words, particularly with models of self- administration of ethanol, it is extremely important to have a read out of the ethanol concentrations that are achieved in brain tissue before, during, and after ethanol consumption (as well as other tissues). Presently available technology does not allow continuous, real-time determination of tissue ethanol concentrations. Our objective is to design, develop, and test an optical fiber probe capable of selective detection of ethanol in vivo. There are three specific aims. Aim 1 will focus on spectrophotometric measurements in order to determine key parameters such as the most suitable optical wavelengths for ethanol measurements, along with sensitivity and detection limits. In addition, potential interferences from other molecules that are present in the brain at relatively high concentrations will be determined. Aim 2 will focus on the design and fabrication of the optical probe. Fiber material, dimensions, measurement configuration and appropriate surface coating will be determined. Aim 3 will focus on in vivo testing in rats that consume ethanol. The obtained optical probe results will be directly compared with standard microdialysis measurements with gas chromatography. Successful development of the proposed ethanol sensing probe for real-time continuous measurement of ethanol in rodent during normal drinking of ethanol would be a significant advance for the field of alcohol research. It will enable more rigorous interpretation of experiment designed to test hypotheses about mechanisms of action of ethanol. Moreover, the applicability of the developed technology will extend beyond ethanol measurements and can be modified for other analytes and applications where microdialysis is used.

项目摘要 酒精使用障碍新疗法的开发需要在以下领域不断取得进展 阐明大脑变化背后的神经药理学机制 重复消耗乙醇产生。为此，包括啮齿动物在内的动物模型 对于进一步了解乙醇暴露如何改变动机至关重要 消耗乙醇。该领域的一个关键限制是监测组织中乙醇的能力（包括 大脑）实时，以便实验者可以解释任何神经生理学或 乙醇产生的神经化学变化。换句话说，特别是对于自我模型 乙醇的管理，读取乙醇的读数非常重要 乙醇消耗之前、期间和之后脑组织中达到的浓度 （以及其他组织）。目前可用的技术不允许连续、实时 组织乙醇浓度的测定。我们的目标是设计、开发和测试 光纤探针能够选择性检测体内乙醇。具体有以下三点 目标。目标 1 将重点关注分光光度测量以确定关键 参数，例如最适合乙醇测量的光波长，以及 具有灵敏度和检测限。此外，来自其他分子的潜在干扰 将以相对较高的浓度存在于大脑中。目标 2 将重点关注 光学探针的设计和制造。纤维材质、尺寸、测量 将确定配置和适当的表面涂层。 Aim 3将专注于体内 在消耗乙醇的大鼠中进行测试。获得的光学探针结果将直接 与使用气相色谱法的标准微透析测量进行比较。成功的 开发所提出的乙醇传感探头，用于实时连续测量 正常饮用乙醇期间啮齿动物体内的乙醇将是该领域的重大进步 酒精研究。它将能够更严格地解释旨在测试的实验 关于乙醇作用机制的假设。此外，所开发的技术的适用性 该技术将扩展到乙醇测量之外，并且可以针对其他分析物进行修改 以及使用微透析的应用。