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Behavioral Core

行为核心

基本信息

批准号：
10469429
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/10469429
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 Clinical Cognition Cognition Disorders Cognitive Cognitive deficits Collection Communities Complex Coupling DSM-V Data Database Management Systems Decision Making Detection Diagnosis Drug abuse Drug usage Emotional Evaluation Exposure to Functional disorder Gender Genetic Grooming Human Impaired cognition Impairment Intake Intellectual impairment International Intervention Lead Lipids Machine Learning Maintenance Marble Maze Learning 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 base behavior measurement behavior test behavioral outcome chronic pain chronic pain patient clinical diagnostics 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 molecular targeted therapies mortality neglect neural circuit neural network neurochemistry novel object recognition opioid epidemic opioid exposure opioid misuse opioid use opioid use disorder pre-clinical psychologic ranpirnase social substance misuse 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病的关键。复杂的神经涉及疼痛和阿片类药物滥用的电路挑战了我们对潜在病理学的理解，潜在的治疗。疼痛患者的认知和决策能力肯定会受损。但用于治疗慢性疼痛患者的阿片类化合物本身也与认知功能有关。损伤尽管阿片类药物使用障碍（OUD）被认为是一种认知障碍，但复杂的在OUD的认知模型中驱动这种行为的神经化学信号仍然不清楚。我们提出了一个 Behavioral Core将Core 3中的神经分析测量与基因编辑的动物协同作用在Core 2中。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同时验证OUD潜在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，十大从人际和自我功能障碍到身体和心理困难，从0-10评分系统上增加阿片类药物的摄入），并将其应用于动物行为测试，临床前成瘾研究的类似评分系统，用于可靠的临床转化应用。这些行为将与核心2和核心3协调执行，以提供最佳的大型数据集，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，以确定新的干预措施在多大程度上显著降低OUD，符合NIH/NIDA的使命。Behavioral Core提供以下预先建立的分析： SA 1-建立成瘾状态的临床前模型，代表OUD的DSM-V标准。 SA 2-建立临床前认知模型，用于评估阿片类药物暴露的后果。 SA 3-将OUD行为评估与动态神经化学收集相结合。阿片类药物流行病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和更好地了解阿片类药物使用和成瘾的神经回路。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。的研究行为核心专门针对成瘾状态下认知功能障碍的潜在回路，决策能力差，吸毒，维持和复发。我们提出的实验实现了多个技术方法，这将允许了解电路介导的认知方面的成瘾状态从核心产生的数据将最终导致假设驱动的NIH/NIDA研究提案，同行审查的出版物、国家和国际介绍以及电子数据库系统，科学界将加速发现有效的治疗OUD的方法。