Thalamic Circuits Underlying Opioid Seeking

摘要 处方阿片类药物滥用是美国增长最快的药物问题。现在，过量服药导致的死亡 阿片类止痛药的比例超过了所有非法药物的比例。长期使用阿片类药物会导致阿片类药物依赖 以戒毒后出现极不愉快的生理和心理症状为特征。 阿片类药物使用者学会将阿片类药物的摄入与从消极的身体和情感状态中解脱联系起来。这 适应不良的联想可能会在戒断后很长一段时间内持续，并成为药物渴望的基础 许多使用者在接触到与毒品有关的线索或应激生活事件后的体验。我们最近做了 证实丘脑室旁核(PVT)是一种重要的神经元底物，介导 伴随阿片类药物戒断的体征和负面情绪，这提供了一个独特的机会 直接研究戒断状态对阿片类药物相关记忆的贡献。在此应用程序中，我们 建议使用路径特定的光遗传和药物遗传操作(1)来确定 PVT输出通路在阿片相关记忆形成和维持中的作用；(2)研究吗啡 每条PVT通路的诱导可塑性以及通路沉默对这种可塑性的影响；(3)我们将结合 PVT、c-Fos iDISCO+和光片荧光显微镜定位中的通路特异性操作 阿片类药物相关记忆的全脑网络活动。我们的工作将激励 治疗阿片类药物滥用的新策略。 安娜·卡罗·德尔·卡斯蒂略将进行研究，为进入生物医学科学生涯做准备。研究行为 可能包括实验室实验、数据收集、数据分析、参加实验室会议、手稿 准备工作和文献综述。她将研究不同动物大脑中c-Fos的表达 各阶段吗啡CPP训练，三维重建c-Fos表达数据集，并对这些数据进行分析 IDISCO地图平台。预计她将在年底就她的研究项目发表正式报告 实习。她将在八(8)周内获得每小时15美元的金额，最高为4,800美元。

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.