Autoradiographic distribution of [3H]YM‐09151‐2, a high‐affinity and selective antagonist ligand for the dopamine D2 receptor group, in the rat brain and spinal cord
- 1 June 1994
- journal article
- Published by Wiley in Journal of Comparative Neurology
- Vol. 344 (1), 121-136
- https://doi.org/10.1002/cne.903440109
Abstract
We determined the regional distribution of the dopamine D2 receptor group in the rat central nervous system by quantitative receptor autoradiography with a high‐affinity and selective antagonist, [3H]YM‐09151‐2. Saturation and competition experiments demonstrated that the binding of [3H]YM‐09151‐2 to striatal sections was saturable (Bmax=37.3 fmol/section), of high affinity (Kd=0.315 nM), and was inhibited selectively by prototypic D2 ligands. The anatomical localization of binding sites was determined by comparison of autoradiograms and the original 3H‐ligand‐exposed sections stained with cresyl violet. Very high levels of [3H] YM‐09151‐2 binding were found in the caudate‐putamen, nucleus accumbens, tuberculum olfactorium and the insula of Calleja, to each of which midbrain dopaminergic neurons project densely. High levels of binding were also observed in other regiions rich in dopaminergic neurons and fibers including the glomerular layer of the olfactory bulb, the intermediate lobe of the pituitary, lateral septum, substantia nigra pars compacta, interfascicular nucleus, dorsal raphe nucleus, locus coeruleus, and nucleus of the solitary tract. Some regions poor in dopaminergi innervation, however, had high levels of [3H]YM‐09151‐2 binding including the molecular layer of gyrus dentatus, all layers of CA1 and the nonpyramidal layer of CA4 of hippocampus, and the deeper layer of medial entorhinal cortex. Motor neurons present in brainstem motor nuclei and spinal ventral horn were also strongly labeled. Neocortical, cerebellar, and thalamic regions had low levels of binding, except lobules 9–10 of the cerebellum, the olivary pretectal nucleus, zona incerta and lateral mammillary nucleus, in which moderate to high levels of binding were detected. Our findings concerning the widespread but region‐specific localization of [3]YM‐09151‐2 binding sites in the brain and spinal cord may prove useful for analyzing varoius dopaminergic functions in the central nervous system.Keywords
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