Center for Opioid and Cocaine Addiction (COCA)

阿片类药物和可卡因成瘾中心 (COCA)

基本信息

批准号：
10017210
负责人：
Peter W Kalivas
金额：
$ 195.86万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
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/10017210
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 Fentanyl Fiber Optics Fostering Genes Genetic Goals HDAC5 gene Heroin Human Immunologics International Intervention Lead Legal Link Mentors Methods Modeling Molecular Morbidity - disease rate Motivation Mus National Institute of Drug Abuse Neurobiology North America Opiate Addiction Opioid Overdose Pathologic Pharmaceutical Preparations Pharmacology Pharmacotherapy Phase Physiology Population Pre-Clinical Model Process Protocols documentation Psychostimulant dependence Quality Control Rattus Reagent Records Relapse Research Research Personnel Research Project Grants Resources Rodent Scientist Self Administration Statistical Data Interpretation Structure Students Substance Use Disorder Synapses System Technology Therapeutic Intervention Training Training Programs Transgenes Transgenic Animals Transgenic Organisms Translating Translations Treatment Protocols Validation Viral Viral Vector Virus Withdrawal Withdrawal Symptom addiction clinical imaging cocaine use craving design differential expression disorder later incidence prevention drug craving drug relapse drug withdrawal heroin use human imaging innovation instrument lens male neurobiological mechanism neuromechanism neuropathology new technology next generation novel novel therapeutic intervention opioid abuse opioid use optogenetics pre-clinical prescription opioid prescription opioid abuse social successful intervention synergism transcriptome sequencing translational approach vector control

项目摘要

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特别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。