Chrna5 knockout mice self-administer more nicotine at high doses than their wild-type littermates (Fowler et al., 2011). Similar to heterozygous Chrna5 mutant mice, the individual with the deletion in exon 2 (Figure 1) may be haplo-insufficient for α5 receptor expression due to NMD of the allele. Thus, without compensatory up-regulation of the other CHRNA5 allele (see below), this heavy smoker may have fewer α5-containing receptors than normal individuals, being able to administer more nicotine for reward, without the aversive consequences of higher nicotine doses.
