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以下方面的持续进展： 阐明大脑变化的神经药理学机制， 重复消耗乙醇产生。为此，动物模型，包括啮齿动物， 在进一步了解乙醇暴露如何改变动机方面至关重要， 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），以便实验者可以解释任何神经生理学或 乙醇引起的神经化学变化。换句话说，特别是对于自我- 因此，在使用乙醇的过程中，读取乙醇的浓度是非常重要的。 在乙醇消耗之前、期间和之后在脑组织中达到的浓度 (as以及其他组织）。目前可用的技术不允许连续的、实时的 组织乙醇浓度的测定。我们的目标是设计、开发和测试 一种可选择性检测体内乙醇的光纤探针。有三个具体的 目标。目标1将集中在分光光度测量，以确定关键 参数，例如用于乙醇测量的最合适的光学波长，沿着 具有灵敏度和检测极限。此外，来自其他分子的潜在干扰， 在大脑中以相对高的浓度存在。目标2将侧重于 光学探针的设计与制作。纤维材料、尺寸、测量 配置和适当的表面涂层将被确定。Aim 3将专注于体内 在消耗乙醇的老鼠身上进行测试。所获得的光学探针结果将直接 与用气相色谱法进行的标准微透析测量相比。成功 开发用于实时连续测量的乙醇传感探头， 在正常饮用乙醇期间啮齿动物中的乙醇将是本领域的重大进展。 酒精研究它将使更严格的解释实验设计测试 关于乙醇作用机制的假说。此外，开发的适用性 该技术将扩展到乙醇测量之外，并可针对其他分析物进行修改 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.