decreased nicotine aversion and that this effect was reversed by viral-mediated expression of the Chrna5 D398N variant in the habenula. Thus, mouse models have helped to elucidate possible roles for two of the genes in the haplotype. Both of these studies examined nicotine self-administration, which is thought to be comparable to self-administration as measured by cigarettes smoked per day in humans. In addition, using a model system, it was possible to manipulate Chrna5 and Chrnb4 expression in the habenula, which provided mechanistic insights about the importance of this brain region, which would have been difficult to obtain using human subjects.
