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 开发用于饮酒障碍的新疗法需要在 阐明神经药理学机制，这些机制是大脑变化的基础 重复的乙醇消耗产生。为此，包括啮齿动物在内的动物模型具有 在进一步了解乙醇暴露如何改变动力的情况下，至关重要 食用乙醇。该领域的关键局限性是监测组织中乙醇的能力（包括 实时的大脑），以便实验者可以解释神经生理学的任何发现或 乙醇产生的神经化学变化。换句话说，尤其是自我模型 乙醇的给药，从乙醇中读出很重要 乙醇消耗之前，期间和之后在脑组织中实现的浓度 （以及其他组织）。目前可用的技术不允许连续实时 测定组织乙醇浓度。我们的目标是设计，开发和测试 能够在体内选择性检测乙醇的光纤探针。有三个特定的 目标。 AIM 1将重点放在分光光度测量上，以确定密钥 沿乙醇测量的最合适的光波长等参数沿 具有灵敏度和检测极限。另外，来自其他分子的潜在干扰 将确定在相对较高浓度的大脑中存在。 AIM 2将重点关注 光学探针的设计和制造。纤维材料，尺寸，测量 将确定配置和适当的表面涂层。 AIM 3将重点放在体内 在食用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值相比。成功的 开发提出的乙醇传感探针以实时连续测量 正常饮用乙醇期间啮齿动物中的乙醇将是该领域的重大进步 酒精研究。它将对旨在测试的实验进行更严格的解释 关于乙醇作用机制的假设。此外，发达的适用性 技术将超越乙醇测量，可以修改其他分析物 以及使用微透析的应用。