The Effects of Nicotine on a Translational Model of Working Memory

尼古丁对工作记忆转化模型的影响

• 批准号: 8316917
• 负责人: David Alderson MacQueen
• 金额: $ 3.74万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-02 至 2014-04-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8316917
• 关键词: Address; Adoption; Animal Model; Animals; Area; Attention; Attention deficit hyperactivity disorder; Behavior Therapy; Behavioral; Cause of Death; Cessation of life; Clinical; Cognition; Cognitive; Cognitive deficits; Consultations; Development; Diagnosis; Diamond; Digit structure; Discrimination; Disease; Dose; Drug abuse; General Population; Goals; Health; High Prevalence; Human; Impairment; Individual; Laboratories; Learning; Letters; Literature; Maintenance; Measures; Mediating; Memory; Mentorship; Methodology; Methods; Modeling; Motivation; Mus; National Institute of Drug Abuse; Neurobiology; Neuropsychology; Neurosciences; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Odors; Participant; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Placebos; Population; Preparation; Procedures; Process; Property; Publications; Radial; Rattus; Reporting; Research; Research Ethics; Research Personnel; Risk; Rodent; Schizophrenia; Short-Term Memory; Site; Smoke; Smoking; Smoking Behavior; Smoking Prevention; Statistical Methods; Strategic Planning; Substance abuse problem; Task Performances; Tobacco; Tobacco smoke; Tobacco smoking; Tobacco use; Training; Water; Work; arm; base; career development; cholinergic; cognitive enhancement; cognitive function; human subject; nicotine gum; non-smoker; non-smoking; novel; response; smoking cessation

DESCRIPTION (provided by applicant): The broad goal of the proposed work is to investigate the potential of cognitive enhancement as a motivator for the escalation and maintenance of tobacco smoking, consistent with aim one of the strategic plan of the National Institute on Drug Abuse (NIDA). Research concerning the effects of nicotine on cognition in non-smokers has demonstrated that nicotine generally enhances attention but not working memory. In contrast, nicotine administration has been shown to produce robust enhancements in working memory in non-human animals. To address this disparity, the present study will investigate the effects of nicotine dose (2mg, 4mg nicotine gum, and placebo) on the performance of non-smokers completing a working memory procedure developed in animals (the odor span task, OST). Nicotine has been demonstrated to enhance OST performance in rodents and the present study will determine whether this effect generalizes to human performance. In addition to completing the OST, participants will complete a cognitive battery comprised of clinical and experimental tasks which assess working memory and attention. This will allow for a direct comparison of OST performance to other commonly used measures of human cognition. An understanding of how OST performance relates to cognitive processing as it is defined in humans will allow researchers to draw stronger inferences about how the neurobiological determinants of OST performance discovered in rats relate to human cognitive processing. Moreover, delineating the cognitive processes enhanced by nicotine in humans is a critical step in determining whether enhancement of cognition mediates the escalation and maintenance of smoking behavior after initiation. As a whole, the project will develop a translational model for assessing the efficacy o novel pharmacological and behavioral interventions for nicotine dependence. This is an important consideration given that the use of tobacco products is the leading cause of preventable death worldwide and causes over 5 million deaths per year. The proposed study builds upon the applicant's prior research investigating the effects of drugs on OST performance in animals, and fits within the applicant's long-term objective of producing translational models of substance abuse and cognition. Towards this end, the applicant has also proposed a training plan directed at building competency in translational behavioral neuroscience. This includes supervised training in the lab of Dr. David Diamond in methods for investigating the neurobiological determinants of learning/memory and drug effects in rodents. Additionally, the applicant will engage in on-site laboratory consultations with experts in the areas of translationa models of substance abuse (Dr. Eric Donny), the neurobiology of human cognition (Dr. Andrew Yonelinas) and the cognitive effects of nicotine (Dr. Stephen Heishman). The applicant will also complete coursework in pharmacology, research ethics, grantsmanship, and statistical methods, and will complete a supervised neuropsychology practicum on the use of cognitive assessments. Lastly, the applicant will receive mentorship from a diverse sponsorship team who will address critical aspects of career development and collaborate in the presentation and publication of research findings. PUBLIC HEALTH RELEVANCE: Tobacco smoking is the leading preventable cause of death worldwide. The development of effective smoking prevention and treatment efforts depend on a thorough understanding of motivations for smoking. The present study seeks to investigate the potential of cognitive enhancement as a motivation for smoking behavior.

描述（由申请人提供）：拟议工作的广泛目标是调查认知增强的潜力，作为升级和维持烟草吸烟的动机，这与AIM一致，这是美国国家药物滥用研究所（NIDA）的战略计划之一。关于尼古丁对非吸烟者认知作用的研究表明，尼古丁通常会增强注意力但没有工作记忆。相比之下，尼古丁给药可在非人类动物的工作记忆中产生强大的增强。为了解决这一差异，本研究将研究尼古丁剂量（2mg，4mg尼古丁口香糖和安慰剂）对完成动物中开发的工作记忆过程（气味跨度任务，OST）的非吸烟者的性能的影响。已经证明尼古丁可以提高啮齿动物的OST性能，本研究将确定这种影响是否概括为人类的表现。除了完成OST外，参与者还将完成由临床和实验任务组成的认知电池，这些任务评估工作记忆和注意力。这将使OST性能与其他常用的人类认知措施进行直接比较。对OST性能与人类定义的认知过程的关系的理解将使研究人员能够对大鼠发现与人类认知处理相关的OST性能的神经生物学决定因素进行更强有力的推断。此外，描述人类中尼古丁增强的认知过程是确定认知增强是否介导开始后吸烟行为的升级和维持的关键步骤。总体而言，该项目将开发一种转化模型，用于评估尼古丁依赖性的新型药理和行为干预措施。鉴于使用烟草产品是全球可预防的死亡的主要原因，并且每年导致超过500万人死亡，这是一个重要的考虑因素。 拟议的研究基于申请人的先前研究，该研究研究了药物对动物OST性能的影响，并符合申请人产生滥用药物和认知模型的长期目标。为此，申请人还提出了一项培训计划，该计划旨在在翻译行为神经科学领域建立能力。这包括在研究啮齿动物中学习/记忆和药物效应的神经生物学决定因素的方法中的戴维·钻石博士实验室的监督培训。此外，申请人将与药物滥用译本（Eric Donny博士），人类认知神经生物学（Andrew Yonelinas博士）和Nicotine的认知效应（Stephen Heishman博士）的专家进行现场实验室咨询。申请人还将完成药理学，研究伦理，授予技巧和统计方法的课程，并将完成有关使用认知评估的监督神经心理学实践。最后，申请人将获得一个多元化的赞助团队的指导，他们将解决职业发展的关键方面，并在研究结果的演示和出版中进行合作。 公共卫生相关性：吸烟是全球可预防的死亡原因。有效的预防吸烟和治疗工作的发展取决于对吸烟动机的透彻理解。本研究旨在研究认知增强的潜力，作为吸烟行为的动机。