It is biologically relevant that the top genetic associations for nicotine dependence were in genes encoding for nicotinic receptor subunits. Nicotine produces its central and peripheral actions by binding to neuronal nicotinic acetylcholine receptors (nAChRs), a class of neuronal ligand-gated ion channels expressed in the nervous system. nAChRs are made of 5 combinations of α and β subunits constructed around a central pore. The subunits are encoded by 9 α (α2–α10) and 3 β (β2–β4) subunit genes, named CHRNA2–CHRNA10 and CHRNB2–CHRNB4, respectively. The expression of the different subunits in specific anatomic areas leads to hypotheses regarding their functional relevance. The addiction of nicotine is believed to arise from the interaction between dopaminergic and nicotinic neurons in the striatum (Fig. 3). Multiple nicotinic subunits are involved in this interaction, including α4, α5, α6, β2, and β3. This region has been implicated in the reward pathway and is important for the development of substance dependence.
