Interrogating the cholinergic basis of opioid use disorder

探究阿片类药物使用障碍的胆碱能基础

基本信息

批准号：
10839681
负责人：
Michael R Tadross
金额：
$ 8.57万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10839681
关键词：
Acetylcholine Action Potentials Acute Address Affect Analgesics Animals Behavior Behavior Disorders Behavioral Brain Cells Clinical Complex Data Development Dopamine Electrophysiology (science)Environment Epidemic Fiber Fostering Future Goals Interneurons Intervention Learning Maps Measurement Measures Mediating Methods Morphine Mus Naloxone Neuromodulator Neuropharmacology Nucleus Accumbens Opioid Opioid Antagonist Opioid Receptor Optics Pain Pain management Parents Pharmaceutical Preparations Pharmacology Phase Photometry Population Positioning Attribute Property Proxy Psychological reinforcement Reagent Research Rest Role Signal Transduction Specificity Surface System Techniques Technology Testing Therapeutic Therapeutic Intervention Viral Vector Work antagonist behavioral study cell type cholinergic clinical efficacy dopaminergic neuron experimental study graduate student insight millisecond mouse model neural neuroregulation novel therapeutic intervention opioid use opioid use disorder parent grant personalized intervention role model sensor side effect temporal measurement tool

项目摘要

ABSTRACT: Diversity Supplement, Interrogating the Cholinergic Basis of Opioid Use Disorder Opioids offer unmatched clinical efficacy in the treatment of pain, yet produce equally harmful side effects that can lead to opioid use disorder. Because traditional drugs impact all cells in a given volume, it has been difficult to map cell type-specific contributions of drug-mediated behavior. To address this gap, we developed an opioid- DART toolset, which makes it possible to deliver clinical opioids to genetically defined cells in behaving mice. In our parent grant, we are now testing the hypothesis that opioid receptors on cholinergic interneurons mediate the harmful (addictive) effects of opioids, independent of helpful (analgesic) effects. This Diversity Supplement supports Lailah Ligons, a rising second-year graduate student, who will examine the cholinergic basis of opioid use disorder with a focus on neural recording. In line with the parent proposal, Lailah's research will involve employing DART technology and behavioral experiments. By focusing on neural recording, her work will provide valuable insights into cell type-specific opioid effects and their impacts on neural activity. Ultimately, this research will contribute to the development of novel therapeutic strategies and further our understanding of the complex interplay between opioids and the brain. Moreover, by promoting diversity in the field of opioid neuropharmacology, this supplement fosters an inclusive research environment and sets the stage for Ms. Ligons to become a role model and future leader in the field.

摘要：多样性补充，探究阿片类药物使用障碍的胆碱能基础阿片类药物在治疗疼痛方面具有无与伦比的临床功效，但也会产生同样有害的副作用，可导致阿片类药物使用障碍。由于传统药物会影响给定体积内的所有细胞，因此很难绘制药物介导行为的细胞类型特异性贡献。为了解决这一差距，我们开发了一种阿片类药物 DART 工具集，可以将临床阿片类药物输送到行为小鼠的基因定义细胞中。在在我们的家长资助下，我们现在正在测试胆碱能中间神经元上的阿片受体介导的假设阿片类药物的有害（成瘾）作用，与有益（镇痛）作用无关。本多样性补充支持莱拉·利根斯 (Lailah Ligons)，她是一名正在崛起的二年级研究生，她将研究阿片类药物的胆碱能基础使用障碍，重点是神经记录。根据家长的提议，莱拉的研究将涉及采用 DART 技术和行为实验。通过专注于神经记录，她的工作将提供关于细胞类型特异性阿片类药物效应及其对神经活动的影响的宝贵见解。最终，这项研究将有助于开发新的治疗策略并加深我们对复杂疾病的理解阿片类药物与大脑之间的相互作用。此外，通过促进阿片类药物领域的多样性神经药理学，该补充品营造了一个包容性的研究环境，并为女士的研究奠定了基础。 Ligons 成为该领域的榜样和未来的领导者。