Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence

Abstract

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also

Current advances in research in treatment and recovery: Nicotine addiction

“…Each receptor is composed of five subunits. Eleven nAChR subunits are expressed in the brain, including α2 to α7, α9, α10, and β2 to β4 ( 36 ). Nicotinic receptors can be heteromeric, with α and β subunits, or homomeric, with five α7 subunits.…”

An ongoing saga of nicotine complexity and dopamine heterogeneity: Nicotine activation and inhibition mediating reward and anxiety

“…This heterogeneity has been characterized in terms of DA neuron firing properties, medial-to-lateral and anterior-to posterior topography, downstream projection targets, and responses to reward, aversion, and stress (Chaudhury et al, 2013;Lammel et al, 2012). However, VTA DA topographic and heterogeneity-specific investigations have rarely been performed in the context of nicotine's actions, despite the extensive evidence that nicotine-mediated reinforcement, reward learning, and addiction results from nicotine-and nicotinic acetylcholine receptor (nAChR)-mediated alterations in cellular processes, firing patterns, intracellular signaling processes, and neuroplasticity within mesolimbic dopamine circuits (Fowler et al, 2020).…”

Multidimensional Intersection of Nicotine, Gene Expression, and Behavior

“…The cholinergic system exerts widespread actions in multiple brain regions to regulate developmental processes, cognition, attention, motivation, reward, sleep, learning, and memory (Lindstrom, 1997;Blake and Boccia, 2018;Mu and Huang, 2019;Fowler et al, 2020;Gipson and Fowler, 2020). Deficits in cholinergic signaling are found to result in a broad range of negative impacts on cognitive processes, such as that found with Alzheimer's disease, Parkinson's disease, and other cognitive disorders (Lindstrom, 1997;Picciotto and Zoli, 2002).…”

“…Deficits in cholinergic signaling are found to result in a broad range of negative impacts on cognitive processes, such as that found with Alzheimer's disease, Parkinson's disease, and other cognitive disorders (Lindstrom, 1997;Picciotto and Zoli, 2002). In the central nervous system, the endogenous neurotransmitter, acetylcholine, is released from axon terminals in all main subdivisions of the brain (Guo et al, 2015;Fowler et al, 2020). Acetylcholine acts on two main receptor subclasses, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs).…”

“…Tobacco cigarettes and e-cigarettes contain high levels of nicotine, which infer a high addiction liability through actions on nAChRs in the reward-related systems in the brain. Activation of nAChRs by nicotine leads to both similar and different actions as that found with acetylcholine, depending on the method of administration, dose, and frequency of exposure (McGehee et al, 1995;Picciotto et al, 2008;Chen et al, 2020;Fowler et al, 2020;Wittenberg et al, 2020). Moreover, in addition to changes in the brain, it should also be noted that long-term effects of nicotine are found in other organ systems, such as the lungs (Ariyoshi et al, 2002;Amos et al, 2008;Garcia-Arcos et al, 2016;Sun et al, 2017;Kyte and Gewirtz, 2018;Liu et al, 2018), although such peripheral actions of nicotine will not be reviewed further herein.…”