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

项目摘要 酒精使用障碍的新疗法的开发需要在 阐明大脑变化背后的神经药理学机制 反复消费乙醇会产生。为此，包括啮齿动物在内的动物模型 对于加深我们对酒精暴露如何改变动机的理解是必不可少的 消耗乙醇。该领域的一个关键限制是监测组织中的乙醇的能力(包括 大脑)，以便实验者能够解释任何神经生理学或 酒精引起的神经化学变化。换句话说，尤其是对于自我的模型 对于乙醇的管理，有一个乙醇读数是极其重要的 酒精摄入前、中、后在脑组织中的浓度 (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 可选择性检测体内乙醇的光纤探头。有三个具体的 目标。目标1将侧重于分光光度测量，以确定关键 参数，如用于乙醇测量的最合适的光学波长，以及 具有灵敏度和检测极限。此外，来自其他分子的潜在干扰 在大脑中以相对较高的浓度存在将被确定。《目标2》将专注于 光学探头的设计与制作。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 在消耗乙醇的大鼠身上进行测试。所获得的光学探头结果将直接 与用气相色谱进行的标准微渗析测量进行了比较。成功 乙醇传感实时连续检测探头的研制 在正常饮用乙醇的情况下，啮齿动物体内的乙醇将是该领域的一个重大进步 酒精研究。它将使人们能够更严格地解释为测试而设计的实验 关于乙醇作用机制的假说。此外，所开发的软件的适用性。 技术将扩展到乙醇测量之外，并可以针对其他分析进行修改 以及使用微透析的应用。

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.