Behavioral Core

行为核心

基本信息

批准号：
10626089
负责人：
Tally Marie Milnes
金额：
$ 43.81万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10626089
关键词：
Address Amalgam Animal Model Animals Arizona Attention Behavior Behavior Disorders Behavior assessment Behavioral Behavioral Assay Biogenic Amines Bioinformatics Biological Assay Brain Chronic Classification Cognition Cognition Disorders Cognitive Cognitive deficits Collection Communities Complex Coupling DSM-V Data Database Management Systems Decision Making Detection Diagnosis Drug abuse Drug usage Electronics Emotional Evaluation Exposure to Functional disorder Gender Genetic Grooming Human Impaired cognition Impairment Intake Intellectual impairment International Intervention Learning Lipids Machine Learning Maintenance Marble Measurement Measures Mediating Memory Methodology Microdialysis Mission Modeling Molecular Molecular Target Morbidity - disease rate National Institute of Drug Abuse Neural Pathways Neuromodulator Neuropharmacology Neurotransmitters Opiate Addiction Opioid Pain Pain Measurement Pain Research Pathology Patients Peer Review Peptides Perception Performance Persistent pain Pharmaceutical Preparations Pharmacology Pre-Clinical Model Process Publications Recording of previous events Relapse Reproducibility Research Research Personnel Research Proposals Rewards Self Administration Signal Transduction Social Interaction Speed Standardization Substance Use Disorder Symptoms System Testing Time United States National Institutes of Health Universities addiction behavior measurement behavior test behavioral outcome chronic pain chronic pain patient clinical diagnostics clinical translation clinically relevant cognitive function conditioned place preference design diagnostic criteria driving behavior effective therapy emotional trauma executive function experimental study genetic approach genetic manipulation in vivo insight large datasets learning strategy mortality neglect neural circuit neural network neurochemistry novel object recognition opioid epidemic opioid exposure opioid misuse opioid use opioid use disorder pre-clinical psychologic social substance misuse synergism translational applications translational potential welfare

项目摘要

Project Summary - Behavioral Core Physical and/or emotional trauma are at the crux of the ongoing pain and opioid epidemics. The complex neural circuitry implicated in pain and opioid misuse challenges our understanding of the underlying pathologies and potential treatments. Cognition and decision-making are certainly impaired in patients with pain. However, the opioids compounds used to treat patients with chronic pain, are themselves also associated with cognitive impairment. Despite the recognition of opioid use disorder (OUD) as a cognitive disorder, the complex neurochemical signaling driving this behavior in cognitive models of OUD remains unclear. We propose a Behavioral Core to synergize the neuro-analytical measurements in Core 3 with the genetically-edited animals in Core 2. This alliance will provide new meaningful insights into the mechanisms of opioid reward and addiction and simultaneously verify new molecular targets and neural pathways underlying OUDs. The Behavioral Core will utilize the DSM-V definition of opioid used disorder (OUD) (i.e., ten major behaviors ranging from inter- and intrapersonal dysfunction to physical and psychological difficulties resulting from increased intake of opioids on a 0-10 scoring system) and apply these to animal behavioral tests to create a similar scoring system for preclinical addiction studies for reliable clinical translational application. These behaviors will be performed in coordination with Cores-2 and Core-3, to provide large data sets optimal for an OUD analysis with bioinformatic and machine learning strategies. In addition, novel molecular targets, therapies and neural networks will be studied to determine to what extent new interventions significantly reduce OUD, in line with the NIH/NIDA mission. The Behavioral Core offer the following pre-established assays: SA1- Establish preclinical models of addictive states that are representative of DSM-V criteria for OUDs. SA2- Establish preclinical models of cognition for evaluation of consequences of opioid exposure. SA3- Integrate OUD behavioral assessment with dynamic neurochemical collection. The escalating number of fatalities from the opioid epidemic necessitates both better interventions to treat OUD and a better understanding of the neural circuits underlying opioid use and addiction. To address this problem, our studies use preclinical animal models based on criteria from human OUD patients. Studies in the Behavioral Core specifically target the circuitry underlying cognitive dysfunction in addictive states that promote poor decision making, drug taking, maintenance and relapse. Our proposed experiments implement multiple technical approaches that will allow for understanding of circuits mediating cognitive aspects of the addictive state. The data generated from the Cores will ultimately lead to hypothesis driven NIH/NIDA research proposals, peer-reviewed publications, national and international presentations and an electronic database system for the scientific community that will speed the discovery of effective therapies for OUD.

项目摘要 - 行为核心身体和/或情感创伤是持续疼痛和阿片类药物流行的症结所在。复杂的神经与疼痛和阿片类药物滥用有关的电路挑战了我们对潜在病理学的理解潜在的治疗方法。疼痛患者的认知和决策肯定会受到损害。然而，用于治疗慢性疼痛患者的阿片类化合物本身也与认知能力有关损害。尽管阿片类药物使用障碍 (OUD) 被认为是一种认知障碍，但复杂的 OUD 认知模型中驱动这种行为的神经化学信号传导仍不清楚。我们提出一个行为核心将核心 3 中的神经分析测量与基因编辑动物相协同核心 2。该联盟将为阿片类药物奖励和成瘾机制提供新的有意义的见解并同时验证 OUD 背后的新分子靶点和神经通路。行为核心将利用 DSM-V 对阿片类药物使用障碍 (OUD) 的定义（即十个主要行为范围从人际关系和内部功能障碍到由此导致的身体和心理困难（根据 0-10 评分系统增加阿片类药物的摄入量）并将其应用于动物行为测试以创建用于临床前成瘾研究的类似评分系统，以实现可靠的临床转化应用。这些行为将与 Cores-2 和 Core-3 协调执行，以提供最适合使用生物信息学和机器学习策略进行 OUD 分析。此外，新的分子靶点、疗法将研究神经网络以确定新干预措施在多大程度上显着减少 OUD，符合 NIH/NIDA 的使命。行为核心提供以下预先建立的检测： SA1-建立代表 DSM-V OUD 标准的成瘾状态临床前模型。 SA2-建立临床前认知模型以评估阿片类药物暴露的后果。 SA3-将 OUD 行为评估与动态神经化学物质收集相结合。阿片类药物流行造成的死亡人数不断增加，需要采取更好的干预措施治疗 OUD 并更好地了解阿片类药物使用和成瘾背后的神经回路。为了解决这个问题为了解决这个问题，我们的研究使用基于人类 OUD 患者标准的临床前动物模型。研究于行为核心专门针对成瘾状态下认知功能障碍的回路，从而促进决策失误、吸毒、维持和复发。我们提出的实验实施了多个技术方法将允许理解介导成瘾认知方面的回路状态。核心生成的数据最终将导致假设驱动的 NIH/NIDA 研究提案，同行评审出版物、国家和国际演示文稿以及电子数据库系统科学界将加速发现 OUD 的有效疗法。