Center for Opioid and Cocaine Addiction (COCA)

项目概要-总体 阿片类药物和可卡因滥用的个人，社会和犯罪后果是巨大的 北美的问题。最可悲的是，海洛因导致的发病率上升， 处方阿片类药物和芬太尼过量在美国。吸毒成瘾通常会 三个阶段，积极吸毒，戒毒和复吸。一 在成瘾循环中，药物干预可能特别有益 是干扰成瘾者复吸的压倒性动机，即使在 急性戒断症状消失后的延长戒断期。然而，在这方面， 复发脆弱性的持久状态来自于相互依赖的大脑适应 在成瘾的所有三个阶段产生。因此，为了发展生物学原理， 治疗复发，不仅需要了解复发本身的神经生物学， 确定给药和停药产生的哪些变化有助于 脆弱性复发的最终持久状态。阿片类药物中心的首要目标是 和COCA成瘾（COCA）是建立和维持科学协同机制， 将有助于发现神经病理学基础的持久和不可控制的 驱动器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个核心的双向转化战略来实现 4个研究项目。除了行政和试点核心，动物和 Validation Core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，并已使用颅内插管、光纤或GRIN器械 透镜。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个项目的范围从确定长期的表观遗传基质， 持久的药物诱导的改变，以了解分子和脑回路机制， 啮齿动物和人类的线索诱导药物寻找。这些项目旨在高度 整合并形成一种双向翻译策略，为新的生物学理论提供生物学基础。 预防复发的治疗方法。

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.