Thalamic Circuits Underlying Opioid Seeking

阿片类药物寻求背后的丘脑回路

基本信息

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
项目类别：
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

项目摘要

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药物问题。现在，服药过量死亡阿片类止痛药超过了所有非法药物。慢性阿片类药物使用诱导阿片类药物依赖性，这终止药物后的生理和心理症状的特征是终止。阿片类药物的用户学会将阿片类药物的摄入与负面的身体和情感状态相关联。这适应不良的协会可能会在撤离终止和渴望的基础后持续很长时间接触药物相关的提示或压力大的生活事件后，许多用户的经验。我们最近有鉴定出丘脑（PVT）的室室核是一种突出的神经元底物，介导身体征兆和负面情绪伴随阿片类药物的提取，这为独特的机会提供了直接检查戒断状态对阿片类药物相关的记忆的贡献。在此应用程序中，我们建议使用途径特定的光遗传学和药物遗传操作（1）来确定 PVT输出途径在形成和维持阿片类药物相关的记忆中；（2）学习吗啡每种PVT途径中的可塑性以及途径沉默对这种可塑性的影响；（3）我们将结合 PVT，C-FOS IDISCO+和光片荧光显微镜的途径特定操作至映射与阿片类药物相关的记忆的脑部全网络活动。我们的工作将激发治疗阿片类药物滥用的新策略。 Ana Caro del Castillo将进行研究，为生物医学科学的职业做准备。研究行为可能包括实验室实验，数据收集，数据分析，参与实验室会议，手稿准备和文献评论。她将检查不同动物的大脑宽C-FOS表达吗啡CPP训练的阶段，3D重建C-FOS表达数据集并用 IDISCO地图平台。预计她将在她的研究项目结束时进行正式演讲实习。在八（8）周内，她将获得每小时$ 15.00的金额，最高为4,800美元。