Pharmacologically defined M1 and M2 muscarinic cholinergic binding sites in the cat's substantia nigra: development...

Muscarinic cholinergic binding in the substantia nigra of the cat was documented during development and at maturity with autoradiographic methods by labeling the pharmacologically defined M1 and M2 subtypes of muscarinic binding sites. In cats from age embryonic day 40 to postnatal day 6 and at adulthood, M1 sites were labeled with [3H]pirenzepine and M2 sites were labeled with [3H]N-methylscopolamine in competition with pirenzepine. Comparisons were made among binding site distributions, acetylcholinesterase staining and tyrosine hydroxylase-like immunoreactivity in serial or neighboring nigral tissue sections. M1 and M2 binding sites were present in the substantia nigra at all ages studied. Qualitative comparisons showed that M1 binding delineated the substantia nigra more distinctly than did M2 binding. For M1 binding sites in particular, the embryonic pars reticulata of the substantia nigra was more prominently labeled than the pars compacta. At adulthood both nigral subdivisions clearly exhibited M1 and M2 binding, with the pars compacta demonstrating some internal heterogeneity of binding density. These findings provide further evidence that the substantia nigra is a site of cholinergic transmission and suggest that the functional balance between acetylcholine and dopamine in the basal ganglia acts here as well as in the striatum.