Center for Opioid and Cocaine Addiction (COCA)

阿片类药物和可卡因成瘾中心 (COCA)

• 批准号: 10404580
• 负责人: Peter W Kalivas
• 金额: $ 196.04万
• 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/10404580
• 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; Lead; 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; Pharmacology; Pharmacotherapy; Phase; Physiology; Population; Pre-Clinical Model; Prescription opioid overdose; Process; Protocols documentation; 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; 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; optogenetics; pre-clinical; prescription opioid abuse; social; stimulant dependence; successful intervention; synergism; 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.

项目概述-整体