Preclinical Models of Nicotine Withdrawal: Targeting Impaired Cognition

Shoaib, M; Hall, FS

doi:10.1016/B978-0-12-802574-1.00003-X

Preclinical Models of Nicotine Withdrawal: Targeting Impaired Cognition

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Abstract

© 2017 Elsevier Inc. All rights reserved. Recent reviews have questioned how we should approach the evaluation of smoking cessation agents in preclinical studies meant to model the effects of those agents in humans, and in particular the role of negative reinforcement and alleviation of negative states by nicotine self-administration (see also Chapter 1 George and by Koob in this volume). This chapter will present evidence from scientific studies on nicotine withdrawal that will highlight the importance of identifying the brain regions activated by antagonist-precipitated withdrawal as potential targets for nicotine cessation treatments by enhancement of cognitive function. It is proposed that optimizing treatments based on restoration of cognitive deficits associated with nicotine withdrawal may provide more effective treatment. For example, clinical success with varenicline may be due to its ability to improve cognitive function, not just as a replacement for nicotine. Cognitive deficits may in fact be drivers of relapse or reduce resistance to factors that trigger relapse in former smokers. Therefore, future preclinical studies on nicotine withdrawal should be designed with more clinically relevant measures of cognition in mind, and cognitive enhancers should be evaluated as putative smoking cessation treatments.