Abstract

Nicotinic acetylcholine receptors (nAChRs) represent an important modulator of striatal function both under normal conditions and in pathological states such as Parkinson's disease. Because different nAChR subtypes may have unique functions, immunoprecipitation and ligand binding studies were done to identify their subunit composition. As in the rodent, α2, α4, α6, β2, and β3 nAChR subunit immunoreactivity was identified in monkey striatum. However, distinct from the rodent, the present results also revealed the novel presence of α3 nAChR subunit-immunoreactivity in this same region, but not that for α5 and β4. Relatively high levels of α2 and α3 subunits were also identified in monkey cortex, in addition to α4 and β2. Experiments were next done to determine whether striatal subunit expression was changed with nigrostriatal damage. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment decreased α6 and β3 subunit immunoreactivity by ∼80% in parallel with the dopamine transporter, suggesting that they are predominantly expressed on nigrostriatal dopaminergic projections. In contrast, α3, α4, and β2 subunit immunoreactivity was decreased ∼50%, whereas α2 was not changed. These data, together with those from dual immunoprecipitation and radioligand binding studies ([³H]cytisine, ¹²⁵I-α-bungarotoxin, and ¹²⁵I-α-conotoxin MII) suggest the following: that α6β2β3, α6α4β2β3, and α3β2^* nAChR subtypes are present on dopaminergic terminals and that the α4β2 subtype is localized on both dopaminergic and nondopaminergic neurons, whereas α2β2^* and α7 receptors are localized on nondopaminergic cells in monkey striatum. Overall, these results suggest that drugs targeting non-α7 nicotinic receptors may be useful in the treatment of disorders characterized by nigrostriatal dopaminergic damage, such as Parkinson's disease.