Genetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction - PubMed (original) (raw)

Review

Genetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction

Yann S Mineur et al. Biochem Pharmacol. 2008.

Abstract

Human twin studies have suggested that there is a substantial genetic component underlying nicotine dependence, ongoing smoking and ability to quit. Similarly, animal studies have identified a number of genes and gene products that are critical for behaviors related to nicotine addiction. Classical genetic approaches, gene association studies and genetic engineering techniques have been used to identify the gene products involved in nicotine dependence. One class of genes involved in nicotine-related behavior is the family of nicotinic acetylcholine receptors (nAChRs). These receptors are the primary targets for nicotine in the brain. Genetic engineering studies in mice have identified a number of subunits that are critical for the ability of nicotine to activate the reward system in the brain, consisting of the dopaminergic cell bodies in the ventral tegmental area and their terminals in the nucleus accumbens and other portions of the mesolimbic system. In this review we will discuss the various lines of evidence suggesting that nAChRs may be involved in smoking behavior, and will review the human and animal studies that have been performed to date examining the genetic basis for nicotine dependence and smoking.

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Figures

Figure 1. Genetically-manipulated mouse models and their relevance for nicotine addiction

Timeline of the reported knockout, knockin of mutations, for various nAChR subunits. Major phenotypes related to nicotine addiction are shown. Please note that the date for generation of the knockout lines may not match the date that the individual phenotypes were reported (see text for detailed paradigms and references). Abbreviations: ↑, increased compared to wild-type controls; ↓, decreased compared to wild-type controls; =, similar to wild-type controls; αCTX MII, α-conotoxin MII; CPP, nicotine conditioned place preference; DA, dopamine; DAT, dopamine transporter; KO, knockout mouse line; KI, knockin mouse line; Loc, chronic nicotine induced locomotor activation; Nic, nicotine; PA, passive avoidance; Self-admin., nicotine self-administration.

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Genetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction - PubMed (original) (raw)