Association of dopamine D1 and D2 receptors with specific cellular elements in the basal ganglia of the cat: the uneven topography of dopamine receptors in the striatum is determined by intrinsic striatal cells, not nigrostriatal axons

Abstract

To ascertain the cellular associations of the D1 and D2 dopamine receptor subtypes in components of the basal ganglia, cats were prepared with unilateral, axon-sparing, ibotenic acid lesions of the striatum (n = 6) or lesions of the nigrostriatal dopamine system by intranigral infusion of 6-hydroxydopamine (n = 8). After 42 days survival, tissue sections from the brains were processed for quantitative, in vitro receptor autoradiography with [3H]SCH23390 (D1 radioligand) or [3H]spiroperidol (D2 radioligand). Lesion-induced changes in basal ganglia nuclei were assessed by comparing them to the corresponding nuclei on the intact side and in naive brains. Ibotenate lesions cause a decline in specific D1 and D2 receptor-binding in the area of the striatal lesion of 94% and 85%, respectively, and completely eliminate the uneven patterns of high- and low-density binding that are characteristic of the cat's caudate nucleus. The globus pallidus, entopeduncular nucleus and pars reticulata of the substantia nigra also show marked reductions in binding after striatal ibotenate lesions. Thus, after caudate nucleus lesions, D2 binding in the two pallidal segments declines by approximately 50%, but remains unchanged in the substantia nigra. Binding of the D1 radioligand (which is not measurable in the globus pallidus) declines by about 75% in the affected regions of the entopeduncular nucleus and pars reticulata, and by about 30% in the pars compacta. Lesions of the nigral dopamine neurons reduce D2 receptor-binding by 95% in the pars compacta and 40% in the pars reticulata, but have no effect on the concentration of D1 or D2 radioligand-binding in the striatum or pallidum. Moreover, such lesions failed to alter the uneven patterns of binding in the striatum. These data suggest that most, if not all, D1 receptors in the basal ganglia are associated with cells of the striatum and their axons in the entopeduncular nucleus and substantia nigra, and likewise, a large majority of D2 receptors are associated with striatal cells and their axons in pallidal structures. Nearly all D2 receptors in the substantia nigra are associated with dopamine neurons (autoreceptors). Finally, the heterogeneous patterns of D1 and D2 receptors in the striatum are a consequence of intrinsic neuronal distributions.