Scholze_2012_J.Neurochem_121_551

Gene association studies in humans have linked the alpha5 subunit gene CHRNA5 to an increased risk for nicotine dependence. In the CNS, nicotinic acetylcholine receptors (nAChRs) that contain the alpha5 subunit are expressed at relatively high levels in the habenulo-interpeduncular system. Recent experimental evidence furthermore suggests that alpha5-containing receptors in the habenula play a key role in controlling the intake of nicotine in rodents. We have now analysed the subunit composition of hetero-oligomeric nAChRs in the habenula of postnatal day 18 (P18) C57Bl/6J control mice and of mice with deletions of the alpha5, the beta2, or the beta4 subunit genes. Receptors consisting of alpha3beta4* clearly outnumbered alpha4beta2*-containing receptors not only in P18 but also in adult mice. We found low levels of alpha5-containing receptors in both mice (6%) and rats (2.5% of overall nAChRs). Observations in beta2 and beta4 null mice indicate that although alpha5 requires the presence of the beta4 subunit for assembling (but not of beta2), alpha5 in wild-type mice assembles into receptors that also contain the subunits alpha3, beta2, and beta4.