Dopamine receptors in human brain: autoradiographic distribution of D1 and D2 sites in Parkinson syndrome of different etiology (original) (raw)
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Dopamine receptors in human brain: Autoradiographic distribution of D2 sites
Neuroscience, 1989
The distribution and density of dopamine D 1 and D 2 receptors were examined by autoradiography in postmortem brain tissue from patients with pathological diagnosis of Parkinson's disease, status lacunaris, clinical parkinsonism without neuropathological lesions and in age-matched controls. The D 1 antagonist [3H]SCH 23390 and the D 2 agonist [3H]CV 205-502 were used as ligands. No significant differences in the distribution or density of D 1 or D 2 receptors were found in Parkinson's disease in the areas examined, including the nucleus caudatus, putamen, globus pallidus and substantia nigra. In contrast, cases presenting lacunar lesions in the striatum showed marked decreases in D 1 and D 2 receptor densities in this region. Patients clinically diagnosed as parkinsonians but without Parkinson's disease lesions or striatal lacunar softenings showed reduced densities of D 2 receptors in the nucleus caudatus and putamen, while in the substantia nigra the densities were comparable to controls. In the basal ganglia of these cases D 1 receptors were slightly decreased.
Dopamine receptors in human brain: Autoradiographic distribution of D1 sites
Neuroscience, 1989
The distribution and density of dopamine D 1 and D 2 receptors were examined by autoradiography in postmortem brain tissue from patients with pathological diagnosis of Parkinson's disease, status lacunaris, clinical parkinsonism without neuropathological lesions and in age-matched controls. The D 1 antagonist [3H]SCH 23390 and the D 2 agonist [3H]CV 205-502 were used as ligands. No significant differences in the distribution or density of D 1 or D 2 receptors were found in Parkinson's disease in the areas examined, including the nucleus caudatus, putamen, globus pallidus and substantia nigra. In contrast, cases presenting lacunar lesions in the striatum showed marked decreases in D 1 and D 2 receptor densities in this region. Patients clinically diagnosed as parkinsonians but without Parkinson's disease lesions or striatal lacunar softenings showed reduced densities of D 2 receptors in the nucleus caudatus and putamen, while in the substantia nigra the densities were comparable to controls. In the basal ganglia of these cases D 1 receptors were slightly decreased.
Dopamine D3 receptor is decreased and D2 receptor is elevated in the striatum of Parkinson's disease
Movement Disorders, 1998
The mesolimbic dopamine (DA) system preferentially innervates the D, receptor, whereas the D, receptor is, in addition, a target of the nigrostriatal DA system. In human brain D, receptors and D, mRNA-expressing neurons are largely segregated to brain regions that are the targets of the mesolimbic DA system and the efferents of the "limbic striatum." Thus, D, receptors may regulate effects of DA on the "limbic" cortico-striatal-pallidal-thalamic-cortical loop. The nigrostriatal DA system is considerably more damaged in Parkinson's disease (PD) than the mesolimbic DA system. We report here, using radioligands selective for the D, and D, receptor, that these receptors are independently changed in PD. Tissue collected at autopsy from nine subjects with a diagnosis of PD and eight age-matched subjects with no evidence of a neurologic disorder was processed for ['2sI]epidepride binding to D, receptors, [1251] trans-7-OH-PIPAT binding to D, receptors, ['2sI]RTI-SS for the DA transporter (DAT), and immuno-
Extrastriatal dopamine D 2 receptors in Parkinson's disease: a longitudinal study
Journal of Neural Transmission, 2003
Most antiparkinsonian drugs are known to act through central dopamine D 2 receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D 2 receptor binding declines at a relatively fast annual rate of 2-4% (compared to the rate of Ͻ1%/year in healthy individuals). In the present study, the examination of longitudinal changes in D 2 receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, ϳ3 years apart, using a high-affinity extrastriatal D 2 /D 3 receptor tracer, [ 11 C]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D 2 -like availabilities (binding potentials) in the left dorsolateral prefrontal cortex, the left temporal cortex and the left and right medial thalami were significantly decreased at the second examination by 20-37% (corresponding to an annual decline of 6-11%). Thus, the annual loss of extrastriatal D 2 availability in PD is up to three times faster than the rate previously reported in the putamen. Our longitudinal study shows first evidence concerning cortical D 2 receptor loss in the progression of PD, although it is not possible to distinguish between the effects of the therapy and the disease.
Journal of the Neurological Sciences, 1988
The densities of D1-and D2-type dopamine receptors were measured with [3H]SCH23390 and [3H]spiperone, in the caudate nucleus and putamen of a large series of patients with Parkinson's disease or progressive supranuclear palsy, in relation to markers of dopaminergic and cholinergic innervation of the striatum ([3H]dihydrotetrabenazine binding and choline acetyltransferase activity). Correlations were sought between these parameters and clinical characteristics of the patients (abnormal involuntary movements, dementia, confusional syndrome or treatment).
Continuous Dopaminergic Stimulation in Parkinson’s Disease
1988
We have investigated the anatomic localization of dopamine D] and D2 receptors in the human brain using selective high affinity ligands for both types of dopamine receptors and the technique of receptor autoradiography. Dopamine D] receptors were labeled in postmortem human brain tissue sections using the antagonist [3H]SCH 23390. Dopamine D2 receptors were labeled in consecutive tissue sections using the agonist eH]205-502 and the antagonist eH]spiroperidol. D] and D2 dopamine receptors presented a heterogeneous distribution in the human brain. The highest concentrations of both D] and D2 receptors were found in parts of the basal ganglia, particularly the nucleus caudatus and putamen. Lower concentrations were seen in other areas for example, the lateral globus pallidus was enriched in D2 receptors and the medial globus pallidus in D] receptors. The substantia nigra contained intermediate densities of both D] and Db D] receptors being present in higher concentrations. Dopamine D] receptors were also localized in areas outside of the basal ganglia, particularly in the neocortex, amygdala and hippocampal formation. Dopamine D2 receptors were also present in areas outside of the basal ganglia, the most significant densities being found in the hippocampal formation. We observed a marked age-dependent decline in the density of D] receptors during the first decades of life. In contrast, D2 receptor concentrations appeared to be unaltered with age. The distribution and densities of dopamine receptors were examined in 12 cases of Parkinson's disease and compared to a control adult population. No significant differences in density and distribution were seen for either D] nor D2 receptors.
Dopamine D1 + D3 receptor density may correlate with parkinson disease clinical features
2020
Dopamine D2‐like receptors – mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) – are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations.
Neuroscience Research Communications, 1996
Patients suffering from Parkinson's disease (PD) display severe and progressive deficits in motor behavior, predominantly as a consequence of the degeneration of dopaminergic neurons, located in the mesencephalon and projecting to striatal regions. The cause of PD is still an enigma. In general, pharmacotherapy comprises symptomatic treatment with dopaminergic compounds, which induce a dramatic initial improvement, although serious problems gradually develop after longterm treatment. This paper describes some recent investigations in pathogenetic, diagnostic and pharmacotherapeutic mechanisms related to dopaminergic systems and PD, as they have been performed in our group.