Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models
Nicotine underlies the reinforcing properties of tobacco cigarettes and e-cigarettes. After inhalation and absorption, nicotine binds to various nicotinic acetylcholine receptor (nAChR) subtypes localized on the pre- and postsynaptic membranes of cells, w
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Contents 1 Introduction 2 nAChR Function and Signaling 3 nAChRs Mediating Nicotine Reinforcement 3.1 Mesolimbic Pathway 3.2 Habenulo-Interpeduncular Pathway 4 nAChRs in Other Aspects of Nicotine Dependence 4.1 Nicotine Enhancement of Cue Association 4.2 Nicotine Withdrawal 5 Modulators of nAChRs Influencing Expression and Function 6 Beyond Nicotine Dependence 7 Conclusions References
Abstract Nicotine underlies the reinforcing properties of tobacco cigarettes and e-cigarettes. After inhalation and absorption, nicotine binds to various nicotinic acetylcholine receptor (nAChR) subtypes localized on the pre- and postsynaptic membranes of cells, which subsequently leads to the modulation of cellular function and neurotransmitter signaling. In this chapter, we begin by briefly reviewing the current understanding of nicotine’s actions on nAChRs and highlight considerations regarding nAChR subtype localization and pharmacodynamics. Thereafter, we discuss the seminal discoveries derived from genetically modified mouse models, which have greatly contributed to our understanding of nicotine’s effects on the reward-related mesolimbic pathway and the aversion-related habenulointerpeduncular pathway. Thereafter, emerging areas of research focusing on modulation of nAChR expression and/or function are considered. Taken together, these
C. D. Gipson Department of Family and Community Medicine, University of Kentucky, Lexington, KY, USA C. D. Fowler (*) Department of Neurobiology and Behavior, University of California, Irvine, CA, USA e-mail: [email protected] © Springer Nature Switzerland AG 2020 Curr Topics Behav Neurosci https://doi.org/10.1007/7854_2020_134
C. D. Gipson and C. D. Fowler
discoveries have provided a foundational understanding of various genetic, neurobiological, and behavioral factors underlying the motivation to use nicotine and related dependence processes, which are thereby advancing drug discovery efforts to promote long-term abstinence. Keywords Addiction · Brain · e-cigarette · Nicotine · Nicotinic acetylcholine receptors (nAChRs) · Tobacco cigarette
1 Introduction Nicotine is the primary active constituent in tobacco-containing products, which is responsible for maintaining smoking behavior in humans (Stolerman and Jarvis 1995). Recently, nicotine has also been formulated for vapor inhalation via e-cigarette devices (Electronic Nicotine Delivery Systems, or ENDS (St Helen et al. 2016)). Concomitant with a decrease in combustible tobacco cigarette use, the use of e-cigarettes, especially among adolescents, has drastically risen in recent years (Wang et al. 2018). Indeed, from 2017 to 2018, there was a rapid increase in vaping prevalence among adolescents aged ~13–18 years old, with nicotine vaping rates translating to roughly an additional 1.3 million adolescent users in 2018 compared to 2017 (Miech et al. 2019). Although e-cigarettes may have value as a nicotine replacement strategy for current tobacco smokers (Hajek et al. 2019), the increasing patterns of e-cigarette use among adolescents have become o
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