CHRNA4 is the gene that encodes the α4 nAChR subunit. The majority of α4 subunits form functional nAChR complexes with at least one β2 subunit and together they account for more than 90% of the high-affinity nicotinic receptors in the brain (Whiting and Lindstrom 1986). α4β2* receptors are expressed in many CNS regions, and α4 mRNA is expressed in nearly every dopaminergic and GABAergic neuron in the VTA, the region affecting dopamine release into the nucleus accumbens. The α4 subunit plays a role in the reinforcing effects of nicotine (Klink et al. 2001), tolerance, and the modulation of mesolimbic dopamine function, all essential to the development of the nicotine dependence phenotype (Tapper et al. 2004).
