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

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 regions 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 dopaminergic 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 [3H]YM-09151-2 binding sites in the brain and spinal cord may prove useful for analyzing various dopaminergic functions in the central nervous system.

Functional dopamine D2 receptors on rat vagal afferent neurones

“…Additionally, phentolamine and propranolol were ineffective in preventing the dopamine-evoked response, discounting the possibility of an action at a-or ,B-adrenoceptors. The temperature-dependence of agonist-induced depolarization of rat vagal afferents has been previously described for angiotensin II (Widdop et al, 1990; (Yokoyama et al, 1994), with the exception that the latter radioligand visualized a population of sites in the hypoglossal nucleus which was not observed in the present study. The reason for this difference is unclear; however, Yokoyama and colleagues (1994) were 'surprised' to observe specific binding of [3H]-YM-09151-2 in a number of brainstem motor nuclei.…”

Electrophysiological properties of catecholaminergic neurons in the norepinephrine-deficient mouse

“…One caveat to this interpretation is that we do not have direct evidence that LC neurons from Dbh −/− mice release DA upon stimulation, although it is highly likely , and we do know that DA is released from Dbh −/− adrenal chromaffin cells (D. Weinshenker and E. Pothos, unpublished observations). Additionally, bath application of dopamine at high concentrations only modestly induces an outward current in both control and Dbh −/−mice, and this effect may be mediated by D2-like receptors (Yokoyama et al, 1994;Suzuki et al, 1998).…”

“…One caveat to this interpretation is that we do not have direct evidence that LC neurons from Dbh −/− mice release DA upon stimulation, although it is highly likely , and we do know that DA is released from Dbh −/− adrenal chromaffin cells (D. Weinshenker and E. Pothos, unpublished observations). Additionally, bath application of dopamine at high concentrations only modestly induces an outward current in both control and Dbh −/−mice, and this effect may be mediated by D2-like receptors (Yokoyama et al, 1994;Suzuki et al, 1998). The LC and other NE nuclei (A1/A2 NE cell region) project directly to, and modulate the activity of, midbrain DA neurons (Swanson and Hartman, 1975;Jones and Moore, 1977;Liprando et al, 2004), and both basal and amphetamine-induced striatal DA release is compromised in Dbh −/− mice (Schank et al, 2005).…”

Pharmacology for the Treatment of Premature Ejaculation

“…D 2 -like receptors have also been detected in limbic areas, hypothalamus, and thalamus. The presence of D 2 /D 3 receptors using radiolabeled ligand in MeA, BNST, and MPOA can be emphasized (Yokoyama et al, 1994;Bancroft et al, 1998).…”