Topography of substantia nigra innervation by D1 receptor-containing striatal neurons

Iodinated SCH 23390, [125I]SCH 23982, saturably binds in brain to D1 receptors that mostly reside on striatal and striatonigral neurons. [125I]SCH 23982 autoradiography was used to determine the topography of D1 receptor-containing striatal inputs to subregions of the substantia nigra. The concentration of D1 sites was greatest in the pars reticulata of the substantia nigra and exceeded by over 50% the equal concentrations of D1 sites in the lateral substantia nigra, caudate-putamen, nucleus accumbens, and olfactory tubercle. D1 receptors were uniformly concentrated throughout the caudate-putamen and were absent in the pars compacta of the substantia nigra and ventral tegmental area. Injections into the rostral striatum of the axon-sparing neurotoxin, quinolinic acid, depleted the concentration of D1 sites in the rostral caudate-putamen by 98% and the concentration of D1 sites in the medial substantia nigra by up to 74%. Quinolinic acid-induced losses of the D1 sites in the central striatum of up to 85% were associated with 87% losses of D1 sites in the central nigra. D1 losses of 91% in the caudal striatum were associated with D1 losses of 85% in the lateral nigra. Thus, most D1 sites in the striatum reside on neurons that are intrinsic to that brain region, and the vast majority of D1 sites in the substantia nigra are on the terminals of striatonigral neurons. These D1 receptor-containing striatonigral neurons have a rostral, central, or caudal origin in the striatum and a corresponding medial, central, or lateral termination in the nigra. This topographical organization of striatal inputs to the substantia nigra indicates that substance P or dynorphin B-containing striatonigral neurons may have D1 receptors on their terminals.