These findings of the α5 nicotinic receptor in humans have motivated further animal studies of this receptor subunit, which show that the habenulo-interpeduncluar pathway is a key neurocircuit controlling nicotine consumption (Fowler et al., 2011). This circuit acts as a negative feedback response, opposite to the mesoaccumbens positive reward pathway. This animal work suggests that individuals with the α5 nicotinic receptor risk alleles for nicotine dependence are relatively insensitive to the inhibitory effects in the reward pathway. This type of work – spanning human, animal, cells and then back to humans - represents the power of genetic studies. We can identify associations, target new genes for study, and then test hypotheses in both animals and man.
