Nicotine dependence is a chronic, relapsing addiction (Lerman et al, 2007), that afflicts >20% of the population worldwide (Fiore et al, 2008). Nicotine exerts its effect primarily at heterogeneous acetylcholine receptors (nAChRs) in the brain. This activity stimulates dopaminergic and other pathways and this increase in dopamine contributes to the rewarding effects of nicotine (Dani and Heinemann, 1996). The principal subtypes of these pentameric receptors include α4 and β2 subunits, sometimes complimented by additional subunits of a different type (eg, α5) (Mineur and Picciotto, 2008; Ray et al, 2010). Nicotine shows high affinity for α4β2-containing nicotinic receptors, with Ki values in the low nanomolar range (Gotti et al, 2006).
