Pilot Project Research Core

先导研究项目核心摘要 试点研究项目核心(PRP)为有兴趣的科学家提供赠款支持和咨询服务 推进药物滥用领域。Pilot Core将鼓励早期调查人员的申请 准备他们的第一个NIDA R01提案。覆检委员会还将与申请者合作，使他们与众多申请者相匹配 中心核心提供的技术服务。Pilot Core还将支持科学家开发新的 促进成瘾研究的技术。为此，我们描述了三个已经准备好的试点项目 以获得支持，并说明PRP的重点。 1)慢性疼痛和阿片类药物暴露之间的相互作用是否会降低认知灵活性？药物滥用 通常伴随着情感和身体上的痛苦。我们小组的数据表明，慢性疼痛会降低执行力 可能导致复发的功能。我们假设慢性疼痛和以前接触阿片类药物会 相互作用，使暴露于慢性疼痛和阿片类药物的动物表现出严重的执行功能下降 并拿出复发的证据。我们将使用行为核心工具来验证这个假设，利用 认知灵活性测试。这些研究将为NIDA R01提案调查提供关键的试点数据 成瘾、慢性疼痛和执行功能之间的相互作用。 2)无线刺激和小鼠神经活动的光度测量：技术 需要选择性地刺激/抑制神经亚型，以确定它们在成瘾中所起的因果作用。 传统的方法使用与动物相连的绳索，这会扰乱行为并损害对 与上瘾相关的行为。该项目支持集成无线技术的开发 光遗传刺激和光度法在不破坏自然动物的情况下测量神经活动 行为。我们计划使用这种设备来刺激和抑制与成瘾相关的神经元。这些 技术将使分析和行为核心受益，因为在 测量和刺激。该项目将使用行为和遗传学核心提供的服务。 3)同时测定行为动物的多巴胺释放和单单位活性。 多巴胺的释放通过触发皮质和纹状体回路的神经可塑性变化来支持学习。上瘾 可能是由于非典型的大量多巴胺释放，增强了对药物相关线索的学习。没有 这一理论的直接证据是，几乎没有同时测量多巴胺释放和 单项作业。我们团队开发了一种在麻醉动物身上使用的系统。这项试点的目标是 建议将该系统用于清醒和行为正常的动物的日常使用，并确定是否具有功能 神经元之间的连接通过阶段性的多巴胺释放而增强。实验将利用以下服务 行为核心和初步数据将用于计划中的NIDA提案。

Summary Pilot Research Project Core The Pilot Research Project Core (PRP) provides grant support and advising services for scientists interested in advancing the field of substance abuse. The Pilot Core will encourage applications from early-stage investigators preparing for their first NIDA R01 proposal. The PRP will also work with applicants to match them with the many technical services offered by the Center Cores. The Pilot Core will also support scientists developing new technologies that advances addiction research. To these ends, we describe three pilot projects that are ready for support and illustrate the focus of the PRP. 1) Do interactions between chronic pain and opioid exposure reduce cognitive flexibility? Drug abuse often follows emotional and physical pain. Data from our group indicates that chronic pain reduces executive function which can contribute to relapse. We hypothesize that chronic pain and previous exposure to opioids will interact such that animals exposed to chronic pain and opioids will exhibit severely reduced executive function and show evidence for relapse. We will test this hypothesis using Behavioral Core facilities, utilizing instrumental tests of cognitive flexibility. These studies will provide key pilot data for a NIDA R01 proposal investigating interactions between addiction, chronic pain, and executive function. 2) Wireless Stimulation and Photometric Measurement of Neural Activity in Mice: Technologies for the selective stimulation/inhibition of neural subtypes are needed to establish the causal roles they play in addiction. Traditional approaches use tethers connected to the animal that disrupt behavior and impair assessment of addiction-associated behaviors. This project supports development of wireless technologies that integrate optogenetic stimulation and photometry for measurement of neural activity without disrupting natural animal behavior. We plan to use this device to stimulate and suppress neurons associated with addiction. These technologies would benefit the Analytical and Behavioral Cores by eliminating the need for tethers during measurement and stimulation. This project will use services provided by the Behavioral and Genetics Cores. 3) Simultaneous Measurement of Dopamine Release and Single-Unit Activity in Behaving Animals. Dopamine release supports learning by triggering neuroplastic changes in cortical and striatal circuits. Addiction may result from atypically large dopamine release that enhances learning of drug-associated cues. There is no direct evidence for this theory as few methods exist for the simultaneous measurement of dopamine release and single-unit activity. Our group developed such a system for use in anesthetized animals. The goal of this pilot proposal is to adapt this system for routine use in awake and behaving animals, and to determine if functional connections between neurons are enhanced by phasic dopamine release. Experiments will utilize services of the Behavioral Core and preliminary data will be used for a planned NIDA proposal.