The alpha 4 beta 2 alpha 5 nicotinic cholinergic receptor in rat brain is resistant to up-regulation by nicotine in vivo

We used immunoprecipitation with subunit-specific antibodies to examine the distribution of heteromeric neuronal nicotinic acetylcholine receptors (nAChRs) that contain the alpha 5 subunit in the adult rat brain. Among the regions of brain we surveyed, the alpha 5 subunit is associated in similar to 37% of the nAChRs in the hippocampus, similar to 24% of the nAChRs in striatum, and 11-16% of the receptors in the cerebral cortex, thalamus, and superior colliculus. Sequential immunoprecipitation assays demonstrate that the alpha 5 subunit is associated with alpha 4 beta 2* nAChRs exclusively. Importantly, in contrast to alpha 4 beta 2 nAChRs, which are increased by 37-85% after chronic administration of nicotine, the alpha 4 beta 2 alpha 5 receptors are not increased by nicotine treatment. These data thus indicate that the alpha 4 beta 2 alpha 5 nAChRs in rat brain are resistant to up-regulation by nicotine in vivo, which suggests an important regulatory role for the alpha 5 subunit. To the extent that nicotine-induced up-regulation of alpha 4 beta 2 nAChRs is involved in nicotine addiction, the resistance of the alpha 4 beta 2 alpha 5 subtype to up-regulation may have important implications for nicotine addiction.