Pilot Project Research Core

试点项目研究核心

• 批准号: 10270351
• 负责人: Stephen Leigh Cowen
• 金额: $ 12.76万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10270351
• 关键词: Advisory Committees; Animal Behavior; Animals; Arizona; Attention; Behavior; Behavioral; Behavioral Genetics; Budgets; Cognitive; Collection; Communication; Conflict of Interest; Core Facility; Corpus striatum structure; Cues; Data; Development; Devices; Dopamine; Drug Addiction; Drug abuse; Electronic Mail; Emotional; Exhibits; Exposure to; Extramural Activities; Feedback; Fostering; Foundations; Funding; Future; Goals; Grant; Impairment; Individual; Learning; Letters; Measurement; Methodology; Methods; Molecular; Mus; National Institute of Drug Abuse; Neural Inhibition; Neurology; Neuronal Plasticity; Neurons; Neurosciences; Opioid; Pain; Pharmaceutical Preparations; Pharmacology; Phase; Photometry; Physiological; Physiology; Pilot Projects; Play; Psychology; Relapse; Research; Research Personnel; Research Project Grants; Resources; Role; Scientist; Services; Substance abuse problem; Summary Reports; System; Technology; Testing; United States National Institutes of Health; Universities; Wireless Technology; Work; Writing; addiction; awake; behavioral study; chronic pain; cognitive testing; executive function; experimental study; flexibility; improved; innovation; interest; meetings; neural circuit; neuroregulation; new technology; novel strategies; opioid exposure; optogenetics; pain reduction; programs; relating to nervous system; service utilization; theories; web site

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.

试点研究项目核心 试点研究项目核心（PRP）为感兴趣的科学家提供资助和咨询服务， 推动药物滥用领域的发展试点核心将鼓励早期研究人员提出申请 准备他们的第一个NIDA R 01提案。PRP还将与申请人合作， 由中心核心提供的技术服务。试点核心还将支持科学家开发新的 这些技术推动了成瘾研究的发展。为此，我们描述了三个准备就绪的试点项目 以支持和说明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 往往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。 这可能会导致复发。我们假设慢性疼痛和先前暴露于阿片类药物将 相互作用，使得暴露于慢性疼痛和阿片类药物的动物将表现出严重降低的执行功能 并有复发的迹象我们将使用行为核心设施来测试这一假设， 认知灵活性测试这些研究将为NIDA R 01提案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)小鼠神经活动的无线刺激和光度测量： 需要神经亚型的选择性刺激/抑制来确定它们在成瘾中所起的因果作用。 传统的方法使用连接到动物的系绳，这会扰乱动物的行为并损害对动物的评估。 成瘾相关的行为。该项目支持无线技术的发展， 不干扰自然动物神经活动的光遗传学刺激和光度测定 行为我们计划用这个装置来刺激和抑制与成瘾有关的神经元。这些 这些技术将使分析核心和行为核心受益，因为它们在执行任务时不需要系绳。 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)行为动物多巴胺释放和单位活动的同时测量。 多巴胺释放通过触发皮层和纹状体回路的神经可塑性变化来支持学习。成瘾 这可能是由于多巴胺的大量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，因为很少有方法同时测量多巴胺的释放， 单位活动。我们的团队开发了这样一个系统，用于麻醉动物。这个试点的目标是 建议是使该系统适用于清醒和行为动物的常规使用，并确定其功能是否正常。 神经元之间的连接通过阶段性多巴胺释放而增强。实验将利用 行为核心和初步数据将用于计划的NIDA提案。