Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse

Abstract

Tobacco-related morbidity and mortality continue to be a significant public health concern. Unfortunately, current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, a better understanding of the neurobiological and neurophysiological mechanisms that promote smoking relapse is needed to develop novel smoking cessation medications. Here, we review preclinical studies focused on identifying the neurotransmitter and neuromodulator systems that mediate nicotine relapse, often modeled in laboratory animals using the reinstatement paradigm, as well as the plasticity-dependent neurophysiological mechanisms that facilitate nicotine reinstatement. Particular emphasis is placed on how these neuroadaptations relate to smoking relapse in humans. We also highlight a number of important gaps in our understanding of the neural mechanisms underlying nicotine reinstatement and critical future directions, which may lead toward the development of novel, target pharmacotherapies for smoking cessation.

A review of tobacco abuse and its epidemiological consequences

“…Similarly, low yield “light” cigarettes and “ultra-light” cigarettes have been designed by different tobacco processing companies, and they are suggested to contain fewer toxins compared to the normal “heavy” cigarettes (Popova et al 2018 ). Elsewhere, a study on nicotine reduction and its associated impacts has pointed out two required lines of action; preventing addiction and reduction or stoppage of tobacco consumption altogether, which never has an easy strategy towards tobacco cessation (Schmidt et al 2018 ). Whereas the use of e-cigarettes and light cigarettes as alternative ways to reduce tobacco toxins may be a successful strategy, controlling thousands of other tobacco toxins released during tobacco burning cannot be achieved by these techniques, which are focused only in lowering nicotine concentration levels in a cigarette (Auer et al 2017 ).…”

Sex Difference in the Association between Electronic Cigarette Use and Subsequent Cigarette Smoking among U.S. Adolescents: Findings from the PATH Study Waves 1–4

“…This study aimed to examine whether and to what extent sex would affect the associations between initial e-cigarette use and subsequent cigarette smoking among American adolescents (aged [12][13][14][15][16][17]. Although the longitudinal associations between e-cigarette use and subsequent cigarette smoking had been documented [8][9][10], no previous studies examined the potential difference in this relationship by sex.…”

“…Sex is a significant dimension for nearly all public health areas [ 13 ], and tobacco use is no exception. Evidence from laboratory experiments with non-human subjects indicated that the neurobiological mechanisms underlying nicotine seeking and metabolism differ between males and females [ 14 , 15 ]. Due to the presence of higher level of estrogen, females metabolize nicotine faster and experience lower rewarding effects of nicotine than males [ 16 ].…”

A 5-Factor Framework for Assessing Tobacco Use Disorder

“…The neurobiological underpinnings of nicotine dependence are complex, and several neurotransmitters, receptors, and pathways are implicated. 2 , 8 , 44 Chronic exposure to nicotine is associated with structural and functional neuroadaptations that drive dependence and promote continued use, 45 as well as pharmacogenetics, and untreated mental health disorders. The age at which someone starts smoking affects the extent of change, with people who started smoking in their teenage or young adult years being the most severely affected.…”