Thalamic Circuits Underlying Opioid Seeking

阿片类药物寻求背后的丘脑回路

• 批准号: 10398490
• 负责人: Xiaoke Chen
• 金额: $ 1.39万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10398490
• 关键词: 3-Dimensional; Affective; Amygdaloid structure; Anatomy; Animals; Automobile Driving; Award; Behavioral; Behavioral Assay; Brain; Brain Mapping; Brain region; Cell Nucleus; Chronic; Cues; Data Analyses; Data Collection; Data Set; Development; Dissection; Dopamine D2 Receptor; Drug usage; Electrophysiology (science); Emotions; Etiology; Event; Exposure to; Extinction (Psychology); FOS gene; Hour; Infusion procedures; Internships; Learning; Life; Light; Link; Maintenance; Manuscripts; Maps; Mediating; Memory; Microscopy; Morphine; Mus; Neurons; Nucleus Accumbens; Opiate Addiction; Opioid; Opioid Analgesics; Output; Parents; Pathway interactions; Pharmaceutical Preparations; Pharmacogenetics; Physiological; Preparation; Protocols documentation; Relapse; Research; Research Project Grants; Retrieval; Review Literature; Role; Science; Structure of paraventricular nucleus of thalamus; Synapses; Synaptic plasticity; Testing; Thalamic structure; Tissues; Training; United States; Viral; Withdrawal; Withdrawal Symptom; Work; base; career; cell type; conditioned place preference; craving; designer receptors exclusively activated by designer drugs; drug craving; drug seeking behavior; experience; experimental study; gain of function; insight; laboratory experiment; loss of function; meetings; microscopic imaging; novel; novel strategies; novel therapeutic intervention; novel therapeutics; opioid abuse; opioid mortality; opioid use; opioid user; opioid withdrawal; optogenetics; prescription drug abuse; prescription opioid abuse; prevent; psychological symptom; reconstruction; relating to nervous system; tool

Abstract Prescription opioid abuse is the fastest growing drug problem in the United States. Now, deaths from overdose of opioid pain relievers exceed those from all illegal drugs. Chronic opioid use induces opioid dependence, which is characterized by extremely unpleasant physiological and psychological symptoms after drug use is terminated. Opioid users learn to associate opioid intake with relief from negative physical and affective states. This maladaptive association might last long after withdrawal has terminated and underlie the drug cravings experience by many users after exposure to drug-associated cues or stressful life events. We have recently identified that the paraventricular nucleus of the thalamus (PVT) is a prominent neuronal substrate mediating the physical signs and negative emotion accompanied with opioid withdrawal, which provide a unique opportunity to directly examine the contribution of withdrawal states to opioid-associated memories. In this application, we propose to use pathway specific optogenetic and pharmacogenetic manipulation (1) to determining roles of the PVT output pathways in the formation and maintenance of opioid-associated memories; (2) to study morphine induced plasticity in each PVT pathway and impact of pathway silencing on this plasticity; (3) we will combine pathway specific manipulation in the PVT, c-Fos iDISCO+, and light sheet fluorescent microscopy to mapping brain-wide network activities underlying opioid-associated memories. Our work will inspire the development of novel strategy to treat opioid abuse. Ana Caro Del Castillo will conduct research to prepare for a career in the biomedical sciences. Research conduct may include laboratory experiments, data collection, data analysis, participation in lab meetings, manuscript preparation, and literature reviews. She will examine brain wide c-Fos expression from animals at different stages of morphine CPP training, 3D reconstruction c-Fos expression dataset and analysis these data with iDISCO map platform. She is expected to deliver a formal presentation on her research project at the end of the internship. She will receive an amount of $15.00 per hour for a maximum of $4,800 for eight (8) weeks.

抽象的 处方阿片类药物滥用是美国增长最快的毒品问题。现在，因服药过量而死亡 阿片类止痛药的用量超过了所有非法药物的用量。长期使用阿片类药物会导致阿片类药物依赖， 其特点是戒毒后出现极其不愉快的生理和心理症状。 阿片类药物使用者学会将阿片类药物的摄入与缓解负面身体和情感状态联系起来。这 戒断结束后，适应不良的关联可能会持续很长时间，并成为药物渴望的基础 许多用户在接触与毒品相关的线索或压力生活事件后的经历。我们最近有 确定丘脑室旁核（PVT）是介导 伴随阿片类药物戒断的身体症状和负面情绪，这提供了一个独特的机会 直接检查戒断状态对阿片类药物相关记忆的贡献。在这个应用程序中，我们 建议使用途径特异性光遗传学和药物遗传学操作（1）来确定 阿片类药物相关记忆形成和维持中的 PVT 输出途径； (2)研究吗啡 每个 PVT 通路中诱导的可塑性以及通路沉默对该可塑性的影响； （3）我们将结合 PVT、c-Fos iDISCO+ 和光片荧光显微镜中的途径特异性操作以进行绘图 阿片类药物相关记忆背后的全脑网络活动。我们的工作将激励发展 治疗阿片类药物滥用的新策略。 安娜·卡罗·德尔·卡斯蒂略 (Ana Caro Del Castillo) 将进行研究，为生物医学领域的职业生涯做好准备。研究行为 可能包括实验室实验、数据收集、数据分析、参加实验室会议、手稿 准备工作和文献综述。她将检查不同时期动物的全脑 c-Fos 表达。 吗啡 CPP 训练阶段、3D 重建 c-Fos 表达数据集并使用以下方法分析这些数据 iDISCO地图平台。预计她将在会议结束时就她的研究项目发表正式演讲 实习。她每小时将收到 15.00 美元的补贴，八 (8) 周内最多可获得 4,800 美元。