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: 8458183
• 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/8458183
• 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; design; 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.

描述（由申请人提供）：拟议工作的总体目标是调查认知增强作为吸烟升级和维持的激励因素的潜力，与国家药物滥用研究所（NIDA）的战略计划之一的目标一致。关于尼古丁对非吸烟者认知能力影响的研究表明，尼古丁通常能增强注意力，但不能增强工作记忆。相比之下，在非人类动物中，尼古丁的使用已被证明对工作记忆产生了强有力的增强。为了解决这一差异，本研究将调查尼古丁剂量（2mg， 4mg尼古丁口香糖和安慰剂）对非吸烟者完成动物工作记忆过程（气味跨度任务，OST）的影响。尼古丁已被证明可以提高啮齿动物的OST表现，本研究将确定这种效应是否适用于人类的表现。除了完成OST之外，参与者还将完成由临床和实验任务组成的认知测试，以评估工作记忆和注意力。这将允许将OST性能与其他常用的人类认知指标进行直接比较。了解OST表现与人类认知处理的关系，将使研究人员能够更有力地推断出在大鼠中发现的OST表现的神经生物学决定因素与人类认知处理的关系。此外，描述尼古丁在人类中增强的认知过程是确定认知增强是否介导吸烟行为开始后的升级和维持的关键步骤。作为一个整体，该项目将开发一个转化模型，以评估对尼古丁依赖的新药理学和行为干预的有效性。这是一个重要的考虑因素，因为烟草制品的使用是全世界可预防死亡的主要原因，每年造成500多万人死亡。拟议的研究建立在申请人先前研究药物对动物OST表现的影响的基础上，并符合申请人建立药物滥用和认知的转化模型的长期目标。为此，申请人还提出了一项培训计划，旨在培养转化行为神经科学的能力。这包括在大卫·戴蒙德博士的实验室进行监督培训，研究啮齿动物学习/记忆和药物作用的神经生物学决定因素。此外，申请人将与药物滥用翻译模型（Eric Donny博士）、人类认知神经生物学（Andrew Yonelinas博士）和尼古丁认知效应（Stephen Heishman博士）等领域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、资助和统计方法的课程，并将完成一项关于认知评估使用的神经心理学实习。最后，申请人将获得来自多元化赞助团队的指导，他们将解决职业发展的关键方面，并在研究成果的展示和出版方面进行合作。