Center for Interdisciplinary Research on Nicotine Addiction (CIRNA)

戒烟会产生令人厌恶的症状，促使复发，通常是在戒烟尝试后的第一周内。因此，阐明这些早期戒断症状的神经生物学和行为基础对于开发更有效的治疗方法至关重要。拟议的尼古丁成瘾跨学科研究中心(CIRNA)延长了宾夕法尼亚大学跨学科烟草使用研究中心(TTURC)进行的九年研究。从临床前研究到临床研究，CIRNA包括一套高度互动的项目和核心，旨在：(1)发现导致复发的早期尼古丁戒断效应的细胞、分子、神经和行为基础；(2)确定有效疗法调节这些过程的大脑和行为机制；以及(3)验证新的药物筛选方法。项目1使用神经生物学和药理学来阐明小鼠模型中尼古丁戒断和重新暴露的情绪和认知症状的分子和行为基础。项目2使用电生理学和药理学来探索尼古丁戒断和重新暴露对小鼠大脑关键区域感觉处理的影响。项目3使用人类神经成像来检查早期戒断症状和药物反应的神经底物。项目4通过验证提高尼古丁依赖早期人类药物筛选范例的敏感性的新方法来扩展这项工作。共享资源，包括一个行政核心、一个数据管理和生物统计核心以及一个生物科学核心，提供增值，并为全面的数据共享计划提供支持。职业发展核心促进博士后研究员和初级调查人员参与这些项目，并支持试点项目以促进职业发展。因此，CIRNA使用创新的多学科方法解决尼古丁依赖这一临床上重要的问题，最终目标是开发更有效的治疗烟草依赖和预防烟草相关疾病的药物。由于美国国立卫生研究院的这一倡议即将结束，因此提议用CIRNA来取代TTURC。

Abstinence from smoking produces aversive symptoms that prompt relapse, often within the first week following a quit attempt. Clarifying the neurobiological and behavioral underpinnings of these early abstinence symptoms is, therefore, critical to develop more efficacious treatments. The proposed Center for Interdisciplinary Research on Nicotine Addiction (CIRNA) extends nine years of research conducted in the Transdisciplinary Tobacco Use Research Center (TTURC) at UPENN. Spanning from preclinical to clinical studies, CIRNA includes a highly interactive set of projects and cores that seek to: (1) discover the cellular, molecular, neural, and behavioral basis of early nicotine abstinence effects that contribute to relapse; (2) identify brain and behavioral mechanisms through which efficacious therapies modulate these processes; and (3) validate novel medication screening approaches. Project 1 uses neurobiology and pharmacology to elucidate the molecular and behavioral basis of emotional and cognitive symptoms of nicotine abstinence and re-exposure in a mouse model. Project 2 uses electrophysiology and pharmacology to explore the effects of nicotine abstinence and re-exposure on sensory processing in key brain regions in mice. Project 3 uses human neuroimaging to examine the neural substrates of early abstinence symptoms and medication response. Project 4 extends this work by validating novel approaches to improve the sensitivity of early human medication screening paradigms for nicotine dependence. Shared resources, including an Administrative Core, a Data Management and Biostatistics Core, and a Biospecimen Core provide value-added, as well as support for a comprehensive data sharing plan. A Career Development Core promotes involvement of post-doctoral fellows and junior investigators in these projects, and supports pilot projects to facilitate career development. Thus, the CIRNA addresses the clinically important problem of nicotine dependence using innovative multidisciplinary approaches, with the ultimate goal of developing more efficacious medications for tobacco dependence and prevention of tobacco-related disease. The CIRNA is proposed to replace the TTURC, since this NIH initiative is ending.