Center for Opioid and Cocaine Addiction (COCA)

项目总结--总体 阿片类药物和可卡因滥用的个人、社会和刑事后果是巨大的。 北美的问题。最可悲的是，海洛因导致的发病率不断上升， 处方阿片类药物和芬太尼在美国过量使用。药物成瘾通常是周期性的 在积极吸毒、戒毒和复吸三个阶段之间。一个 成瘾循环中的一个时间点，药物干预特别有益 是干扰吸毒者重新吸毒的压倒性动机，即使在 当急性戒断症状消散时的长时间戒断。然而， 复发易感性的持久状态源于相互依赖的大脑适应 在上瘾的三个阶段都会产生。因此，为了发展生物学原理， 治疗复发，不仅有必要了解复发本身的神经生物学，而且有必要 确定给药和停药导致的变化 故态复萌的最后一种持久状态。阿片类药物中心的首要目标 和可卡因成瘾(Coca)是为了创造和维护科学协同机制， 将有助于发现支撑持久的和不可控制的 推动寻找阿片类药物和可卡因，从而推进 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个核心的双向转换战略来实现 和4个研究项目。除了行政和试点核心外，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进行过手术 镜头。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链霉菌的表观遗传底物。 持续药物诱导的改变，以了解分子和脑电路机制 线索在啮齿动物和人类中诱导的药物寻找。这些项目被设计成高度 整合并形成双向翻译策略，为新词提供生物学基础 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.