The Effects of Nicotine on a Translational Model of Working Memory

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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.