Center for Opioid and Cocaine Addiction (COCA)

阿片类药物和可卡因成瘾中心 (COCA)

• 批准号: 10630221
• 负责人: Peter W Kalivas
• 金额: $ 195.69万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10630221
• 关键词: Abstinence; Acute; Animal Model; Animals; Antioxidants; Astrocytes; Behavior; Behavior Control; Biological; Brain; Cannulas; Cell physiology; Cells; ChIP-seq; Clinical; Clinical Protocols; Cocaine; Cocaine Abuse; Cocaine Dependence; Cocaine Users; Core Facility; Cues; DSM-V; Databases; Development; Drug Addiction; Drug usage; Drug user; Education and Outreach; Environment; Epigenetic Process; Experimental Designs; Extracellular Matrix; Faculty; Female; Fiber Optics; Fostering; Genes; Genetic; Goals; HDAC5 gene; Heroin; Human; Immunologics; International; Intervention; Legal; Link; Mentors; Methods; Modeling; Molecular; Morbidity - disease rate; Motivation; Mus; National Institute of Drug Abuse; Neurobiology; North America; Opiate Addiction; Opioid; Pathologic; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiology; Population; Pre-Clinical Model; Prefrontal Cortex; Prescription opioid overdose; Process; Protocols documentation; Quality Control; Rat Transgene; Reagent; Records; Relapse; Research; Research Personnel; Research Project Grants; Resources; Rodent; Scientist; Self Administration; Statistical Data Interpretation; Structure; Students; Substance Use Disorder; Synapses; Technology; Therapeutic Intervention; Training; Training Programs; Transgenes; Transgenic Animals; Transgenic Organisms; Translating; Translation Process; Translations; Treatment Protocols; Validation; Viral; Viral Vector; Virus; Withdrawal; Withdrawal Symptom; addiction; clinical imaging; cocaine use; craving; design; differential expression; drug craving; drug relapse; drug withdrawal; fentanyl overdose; heroin overdose; heroin use; human imaging; innovation; instrument; lens; male; neurobiological mechanism; neuromechanism; neuropathology; new technology; next generation; novel; novel therapeutic intervention; opioid abuse; opioid use; optical fiber; optogenetics; pharmacologic; pre-clinical; prescription opioid abuse; relapse prevention; social; stimulant dependence; successful intervention; synergism; technology platform; transcriptome sequencing; translational approach; vector control

PROJECT SUMMARY - Overall The personal, social and criminal consequences of opioid and cocaine abuse are enormous problems in North America. This is most tragically seen in rising morbidity due to heroin, prescription opioids and fentanyl overdose in the USA. Addiction to drugs typically cycles between three phases, active drug use, withdrawal from drug use and relapse to drug use. A point in the cycle of addiction where pharmacological intervention can be particularly beneficial is to interfere with the overwhelming motivation by addicts to relapse to drug use, even after extended periods of abstinence when acute withdrawal symptoms have dissipated. However, the enduring state of relapse vulnerability arises from interdependent brain adaptations produced during all three phases of addiction. Thus, in order to develop biological rationales for treating relapse, it is necessary to understand not only the neurobiology of relapse itself, but to determine which changes produced by drug administration and drug withdrawal contribute to the final enduring state of relapse vulnerability. The overarching goal of the Center for Opioid and Cocaine Addiction (COCA) is to create and maintain mechanisms of scientific synergy that will facilitate discovering the neuropathologies that underpin the enduring and uncontrollable drive to seek opioids and cocaine, and thereby advance biological rationales needed to efficiently generate pharmacotherapies that inhibit drug relapse. This goal will be achieved through a bidirectional translational strategy that involves 3 Cores and 4 research Projects. In addition to the Administrative and Pilot Cores, the Animal & Validation Core makes available transgenic rodents that have been trained to self-administer heroin or cocaine, and have been instrumented with intracranial cannulae, fiber optics or GRIN lens. This Core will also validate all viral reagents and transgenic animals shared by the COCA Cores and Projects. The 4 Projects range from determining the epigenetic substrates of long- lasting drug-induced alterations to understanding the molecular and brain circuit mechanisms of cue-induced drug seeking in rodents and humans. The Projects are designed to be highly integrated and form a bidirectional translation strategy for providing biological rationales for new therapeutic approaches to relapse prevention.

项目概要 - 总体 阿片类药物和可卡因滥用对个人、社会和犯罪造成的后果是巨大的 北美的问题。最悲惨的是海洛因导致的发病率上升， 美国处方阿片类药物和芬太尼过量。药物成瘾通常会循环 三个阶段之间，即主动吸毒、戒断吸毒和复发吸毒。一个 成瘾周期中药物干预尤其有益的点 是为了干扰成瘾者重新吸毒的强烈动机，即使是在吸毒之后 当急性戒断症状消失后，延长禁欲期。然而， 复发脆弱性的持久状态源于相互依赖的大脑适应 在成瘾的所有三个阶段中都会产生。因此，为了开发生物学原理 治疗复发，不仅需要了解复发本身的神经生物学，还需要了解 确定给药和停药产生的哪些变化有助于 复发脆弱性的最终持久状态。阿片类药物中心的总体目标 和可卡因成瘾（COCA）的目的是建立和维持科学协同机制， 将有助于发现支撑持久且无法控制的神经病理学 推动寻求阿片类药物和可卡因，从而推进所需的生物学原理 有效地产生抑制药物复发的药物疗法。 这一目标将通过涉及 3 个核心的双向转化策略来实现 和4个研究项目。除了行政和试点核心之外，动物和 验证核心提供经过自我管理训练的转基因啮齿动物 海洛因或可卡因，并装有颅内插管、光纤或 GRIN 镜片。该核心还将验证 COCA 共享的所有病毒试剂和转基因动物 核心和项目。这 4 个项目的范围包括确定长链的表观遗传底物 持久的药物引起的改变，以了解分子和脑回路机制 啮齿类动物和人类中线索诱导的药物寻找。这些项目的设计高度 整合并形成双向翻译策略，为新的研究提供生物学原理 预防复发的治疗方法。