Identification of the Nicotinic Receptor Subtypes Expressed on Dopaminergic Terminals in the Rat Striatum

Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) expressed on mesostriatal dopaminergic neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Using immunoprecipitation and ligand-binding techniques, we have shown that both α6β2* and α4(nonα6)β2* nAChRs are expressed in the caudate–putamen and that only α6* nAChRs can bind α-conotoxin MII and methyllycaconitine with affinities of 1.3 and 40 nm, respectively. Further studies performed on 6-hydroxydopamine-lesioned striatum led to the identification of nAChR subtypes selectively expressed on dopaminergic terminals [α4α5β2, α4α6β2(β3), and α6β2(β3)], nondopaminergic neuronal structures (α2α4β2), or both structures (α4β2). The identification of the nAChRs expressed on striatal dopaminergic terminals opens up the possibility of developing selective nAChR ligands active on dopaminergic systems and associated diseases, such as Parkinson9s disease.

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