Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson's disease and progressive supranuclear palsy: A quantitative autoradiographic study using [ 3H]mazindol

Abstract

It has been suggested that not only mesostriatal but also mesolimbic pathways are involved in the degeneration of dopaminergic neurons in Parkinson's disease. Using quantitative ligand autoradiography we have investigated dopamine transporter sites in basal ganglia of patients affected by Huntington's chorea, Parkinson's disease and progressive supranuclear palsy. [ 3H]Mazindol, a ligand for catecholamine uptake, was used in the presence of desipramine to block the binding to norepinephrine uptake sites. Schizophrenic cases were entered in the study to take into account the effects of neuroleptics, commonly administered also to Huntington's disease patients, on dopamine uptake sites. In control cases high densities of [ 3H]mazindol binding sites were found in the caudate nucleus, putamen and nucleus accumbens, whereas very low densities were present in substantia nigra and ventral tegmental area. In Huntington's chorea the density of [ 3H]mazindol binding sites was slightly decreased in the caudate nucleus, an area severely affected by the neurodegenerative process. In schizophrenic patients the density of dopamine uptake sites in the basal ganglia was slightly reduced, mainly in the middle third of putamen. Both Parkinson's disease and progressive supranuclear palsy populations were characterized by a marked loss of [ 3H]mazindol binding sites in the neostriatum (about 75%) and in the nucleus accumbens (about 65%). These results suggest that in Parkinson's disease and progressive supranuclear palsy severe decreases of dopamine uptake sites occur not only in the mesostriatal pathway but also in the mesolimbic tract.