University of Washington Center of Excellence in Opioid Addiction Research

华盛顿大学阿片类药物成瘾研究卓越中心

• 批准号: 10611870
• 负责人: Charles Chavkin
• 金额: $ 132.76万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10611870
• 关键词: Address; Affect; Animals; Anxiety Disorders; Award; Behavior; Behavioral; Brain; Brain imaging; CRISPR/Cas technology; Calcium Signaling; Canis familiaris; Cells; Collaborations; Communities; Complex; Computer Analysis; Confocal Microscopy; Coupled; DSM-V; Development; Disease; Drug Addiction; Drug usage; Education and Outreach; Educational workshop; Endoscopy; Ensure; Fiber; Fostering; Funding; Gene Expression; Genetic; Genetic Techniques; Goals; Image; Imaging Device; Infrastructure; Institution; Investigation; Laboratories; Light; Link; Mental Depression; Methodology; Modernization; Molecular; Molecular Genetics; Monitor; Morphine; Mus; National Institute of Drug Abuse; Neurobiology; Neurons; Neurosciences; Opiate Addiction; Opioid; Pain; Participant; Photometry; Photons; Pilot Projects; Postdoctoral Fellow; Productivity; Qualifying; Rattus; Reagent; Receptor Signaling; Recording of previous events; Reproducibility; Research; Research Personnel; Resolution; Resource Sharing; Resources; Risk; Rodent; Rodent Control; Scientist; Self Administration; Substance Use Disorder; Techniques; Training; Training and Education; United States National Institutes of Health; Universities; Viral; Viral Genes; Visit; Visualization; Washington; addiction; archive data; awake; comorbidity; computational neuroscience; computerized tools; data analysis pipeline; design; design and construction; drug abstinence; dysphoria; genetic manipulation; genetic resource; graduate student; imaging approach; imaging genetics; in vivo; innovation; insight; meetings; motivated behavior; neural circuit; neuroimaging; novel; novel therapeutics; open data; opioid use; opioid use disorder; optogenetics; outreach; recruit; relapse risk; research study; sensor; tool; two photon microscopy; two-photon; undergraduate student; vector; web site

Overall Summary The “University of Washington Center of Excellence in Opioid Addiction Research” is designed to provide shared resources that would enhance efficiency and facilitate collaborative research for the study of the effects of opioids on neural circuits with the goal of understanding opioid addiction mechanisms and developing novel treatments for drug addiction. Center participants from 16 UW laboratories are using optogenetic control of rodent behavior, in vivo neuroimaging of single cell calcium signals and other receptor signaling probes, viral gene expression and CRISPR/cas9 manipulations to deconstruct and study opioid self-administration. This group has a long-history of highly productive, collaborative, cutting-edge research and training that will be strengthened by the shared resources provided by this award. The proposed Center would be comprised of four components: The Administrative Core will coordinate resource utilization, organize monthly Research Progress Meetings, organize training and outreach efforts. The Imaging and Neural Circuits Core would develop shared resources for in vivo brain imaging in rats and mice using 1-Photon endoscopy, Inscopix imaging, 2-Photon confocal microscopy, Spatial Light Modulation, fiber photometry and operant behaviors. The Molecular Genetics Resource Core would provide DIO-AAV / CRISPR-cas9 / Canine Adeno Viral reagents, develop new activity actuators and sensors and provide advanced training in cell-specific genetic manipulation coupled with behavioral and computational analysis. A Pilot Project Core would enable participants and trainees to initiate new projects utilizing the Imaging and Genetic Cores and would foster training and collaborations within the Center laboratory groups and university community at large. The Center would become a national neuroscience resource by providing training to visiting scientists, reagents for genetic manipulation and novel actuators/sensors on request from investigators at other institutions. It will provide workshops and summer courses for training advanced undergraduate and graduate students in optogenetics, computational neuroscience, and viral design & construction techniques. All of these components would be focused on understanding the changes in neural circuitry responsible for opioid addiction and on the development of new therapeutic tools based on these insights.

总体摘要 “华盛顿大学阿片成瘾研究卓越中心”旨在提供 共享资源，以提高效率和促进研究影响的协作研究 阿片类药物在神经回路上的研究，目的是了解阿片成瘾机制和开发新的阿片成瘾药物 药物成瘾的治疗。来自威斯康星州16个实验室的中心参与者正在使用光基因控制 啮齿动物行为，单细胞钙信号和其他受体信号探针的体内神经成像，病毒 基因表达和CRISPR/Cas9操作解构和研究阿片类药物自我给药。这 集团在高效、协作、尖端的研究和培训方面有着悠久的历史，将 这一奖项所提供的共享资源加强了这一点。拟建的中心将由以下人员组成 四个组成部分：行政核心将协调资源利用，组织每月研究 推动会议进展，组织培训和外联工作。成像和神经电路核心将 利用单光子内窥镜技术开发大鼠和小鼠体内脑成像的共享资源 成像，双光子共聚焦显微镜，空间光调制，纤维光度学和操作行为。这个 分子遗传学资源核心将提供DIO-AAV/CRISPR-Cas9/犬腺病毒试剂， 开发新的活动致动器和传感器，并提供细胞特异性基因操作方面的高级培训 再加上行为和计算分析。试点项目核心将使参与者和 受训人员利用成像和遗传核心发起新项目，并将促进培训和 中心实验室小组和整个大学社区之间的合作。该中心将 通过为来访的科学家、基因试剂提供培训，成为国家神经科学资源 应其他机构研究人员的要求，提供操控和新颖的致动器/传感器。它将提供 培训光遗传学高级本科生和研究生的工作坊和暑期课程， 计算神经科学，以及病毒设计和建造技术。所有这些组件都将是 重点是了解导致阿片成瘾的神经回路的变化以及 基于这些见解开发新的治疗工具。

项目成果

Recapitulating phenotypes of alcohol dependence via overexpression of Oprk1 in the ventral tegmental area of non-dependent TH::Cre rats.

通过在非依赖性 TH::Cre 大鼠腹侧被盖区过度表达 Oprk1 来概括酒精依赖性表型。

• DOI: 10.1016/j.neuropharm.2023.109457
• 发表时间: 2023
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Lepreux,Gaetan;Shinn,GraceE;Wei,Gengze;Suko,Azra;Concepcion,George;Sirohi,Sunil;SoonGo,Bok;Bruchas,MichaelR;Walker,BrendanM
• 通讯作者: Walker,BrendanM

Kappa-opioid receptor activation reinstates nicotine self-administration in mice.

Kappa-阿片受体激活可恢复小鼠尼古丁的自我给药。

• DOI: 10.1016/j.addicn.2022.100017
• 发表时间: 2022
• 期刊: Addiction neuroscience
• 作者: Gowrishankar,Raajaram;Gomez,Adrian;Waliki,Marie;Bruchas,MichaelR
• 通讯作者: Bruchas,MichaelR

A unique role for cAMP signaling in microglia during opioid tolerance and withdrawal.

阿片类药物耐受和戒断期间小胶质细胞中 cAMP 信号传导的独特作用。

• DOI: 10.1038/s41386-023-01685-2
• 发表时间: 2024
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Coffey,KevinR;Neumaier,JohnF
• 通讯作者: Neumaier,JohnF

Satb2 neurons in the parabrachial nucleus mediate taste perception.

• DOI: 10.1038/s41467-020-20100-8
• 发表时间: 2021-01-11
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Jarvie BC;Chen JY;King HO;Palmiter RD
• 通讯作者: Palmiter RD

A genetic variant of fatty acid amide hydrolase (FAAH) exacerbates hormone-mediated orexigenic feeding in mice.

• DOI: 10.7554/elife.81919
• 发表时间: 2023-04-11
• 期刊: eLife
• 影响因子: 7.7
• 作者: Balsevich G;Petrie GN;Heinz DE;Singh A;Aukema RJ;Hunker AC;Vecchiarelli HA;Yau H;Sticht M;Thompson RJ;Lee FS;Zweifel LS;Chelikani PK;Gassen NC;Hill MN
• 通讯作者: Hill MN