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 habenulo-interpeduncular pathway. Thereafter, emerging areas of research focusing on modulation of nAChR expression and/or function are considered. Taken together, these 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.

The idea that interconnected neuronal ensembles code for specific behaviors has been around for decades; however, recent technical improvements allow studying these networks and their causal role in initiating and maintaining behavior. In particular, the role of ensembles in drug-seeking behaviors in the context of addiction is being actively investigated. Concurrent with breakthroughs in quantifying ensembles, research has identified a role for synaptic glutamate spillover during relapse. In particular, the transient relapse-associated changes in glutamatergic synapses on accumbens neurons, as well as in adjacent astroglia and extracellular matrix, are key elements of the synaptic plasticity encoded by drug use and the metaplasticity induced by drug-associated cues that precipitate drug-seeking behaviors. Here, we briefly review the recent discoveries related to ensembles in the addiction field and then endeavor to link these discoveries with drug-induced striatal plasticity and cue-induced metaplasticity toward deeper neurobiological understandings of drug seeking.

Introduction

Scientific discoveries over the past few decades have provided significant insight into the abuse liability and negative health consequences associated with tobacco and nicotine-containing products. While many of these advances have led to the development of policies and laws that regulate access to and formulations of these products, further research is critical to guide future regulatory efforts, especially as novel nicotine-containing products are introduced and selectively marketed to vulnerable populations.

Discussion

In this narrative review, we provide an overview of the scientific findings that have impacted regulatory policy and discuss considerations for further translation of science into policy decisions. We propose that open, bidirectional communication between scientists and policy makers is essential to develop transformative preventive- and intervention-focused policies and programs to reduce appeal, abuse liability, and toxicity of the products.

Conclusions

Through these types of interactions, collaborative efforts to inform and modify policy have the potential to significantly decrease the use of tobacco and alternative nicotine products and thus enhance health outcomes for individuals.

Implications

This work addresses current topics in the nicotine and tobacco research field to emphasize the importance of basic science research and provide examples of how it can be utilized to inform public policy. In addition to relaying current thoughts on the topic from experts in the field, the article encourages continued efforts and communication between basic scientists and policy officials.