The difficulty people experience in quitting smoking is an expression of nicotine addiction. The reinforcing actions of nicotine are mediated by binding to nicotinic acetylcholine receptors (nAChRs) in the central nervous system. nAChRs are ligand-gated ion channels that respond to the neurotransmitter acetylcholine (ACh), as well as to nicotine. Chronic exposure of nAChRs to nicotine stabilizes a desensitized, closed state, decreasing receptor function, and increases the assembly of high-affinity receptors (2). Assembled, functional nAChRs are composed of combinations of five subunits that are encoded by 17 genes. In the brain, the majority of nAChRs are composed of α4β2 hetero-oligomers that have high affinity for nicotine (3).
