ChAT is responsible for the synthesis and modulation of endogenous acetylcholine (Whittaker 1988). ChAT influences several cholinergic-dependent functions including cognitive performance (Bacciottini et al. 2001) and has been shown to mediate modulatory effects cholinergic receptors on mesocorticolimbic dopaminergic pathways (Gronier et al. 2000). Chronic nicotine administration in adult rats has been shown to increase ChAT enzyme activity (Hernandez and Terry 2005) and ChAT enzyme activity is altered during nicotine withdrawal in adolescent animals (Slotkin et al. 2008). Molecules that alter ChAT enzyme activity have been tested clinically. Galantamine, an acetyl-cholinesterase inhibitor that increases the concentration of acetylcholine, may reduce smoking behavior (Diehl et al. 2006) suggesting that ChAT is a biologically plausible candidate gene for smoking behavior phenotypes.
