The psychopharmacologic effects of nicotine are mediated primarily by functionally diverse neuronal nicotinic acetylcholine receptors (nAChRs), a family of ligand-gated ion channels widely distributed in the brain (Gaimarri and others 2007; Picciotto and others 2000; Watkins and others 2000). These nAChRs are involved in numerous physiological functions both in the brain and in the periphery as well (Gotti and Clementi 2004). To date, 12 neuronal nAChR subunits have been identified, consisting of nine α (α2-α10) and three β (β2-β4) subunits. The human genes for all of these subunits except α8 have been cloned (Graham and others 2002). The 11 nAChR subunit genes are located on chromosomes 1, 4, 8, 11, 15, and 20. Of these, CHRNA5, CHRNA3, and CHRNB4 are grouped in a cluster on chromosome 15q24 (Raimondi and others 1992), in which CHRNA3 and CHRNA5 are located in a tail-to-tail configuration on opposite DNA strands and share some of their 3′-untranslated region (Duga and others 2001). Similarly, CHRNB3 and CHRNA6 are grouped in a cluster on chromosome 8p11. The clustered arrangement of CHRNA5/A3/B4 and CHRNB3/A6 could be related to control of the expression of these genes (Flora and others 2000; Xu and others 2006).
