Nicotine pharmacology, abuse, and addiction

Abstract

Despite increased public awareness of the substantial health risks, tobacco use remains one of the greatest public health concerns around the world. Although cultural influences contribute to tobacco use, the principal reason for sustained tobacco use is the highly addictive nature of nicotine, its primary psychoactive component. One in three individuals who try tobacco will become addicted, and more people use tobacco than any other drug of abuse. Thus, research into the neurobiological mechanisms of nicotine addiction is of great public health relevance, and decades of clinical and pre-clinical studies have substantially improved our understanding of these processes. Like other drugs of abuse, the addictive properties of nicotine are mediated through the mesolimbic dopamine system, where it exerts its reinforcing and rewarding effects. Nicotine acts through specific interactions with nicotinic acetylcholine receptors (nAChRs), a class of ionotropic neurotransmitter receptors expressed throughout the brain. Because of the broad expression of these nAChRs, nicotine exerts broad effects on the nervous system that likely underlie its high degree of co-morbidity with other neuropsychiatric disorders. In this chapter we will discuss our current understanding of how nicotine acts through nAChRs to promote the cellular and physiological changes underlying the behavioral manifestations of tobacco use. We will also consider developmental consequences of nicotine exposure, coincidence of nicotine use with other neuropsychiatric disorders, and current challenges in the field of nicotine and tobacco research.