Alterations in striatal and extrastriatal D‐1 and D‐2 dopamine receptors in the MPTP‐treated common marmoset: An autoradiographic study

In adult common marmosets (Callithrix jacchus), MPTP (1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine) treatment induced almost total depletion of cells in the substantia nigra pars compacts (SNc) but partial cell loss in the ventral tegmental area (VTA). There was severe depletion of [³H]‐mazindol binding to dopamine (DA) uptake sites in the caudate, putamen, and SNc. The loss of [³H]‐mazindol binding in the nucleus accumbens (NAc) and olfactory tubercle (OT) was less marked. [³H]‐mazindol binding in the body of caudate nucleus showed a small but significant recovery with increasing post‐lesion survival times. The specific binding of [³H]‐SCH 23390 to D‐1 DA receptor sites was increased after MPTP treatment in all subregions of both caudate and putamen but was unaltered in the NAc and OT. Substantia nigra pars reticulata (SNr), frontal cortex, and medial segment of globus pallidus (GPm) all demonstrated moderate levels of [³H]‐SCH 23390 binding in control animals, which were unaffected by MPTP treatment. Specific [³H]‐spiperone binding to D‐2 DA receptor sites was not altered by MPTP treatment in the subregions of caudate‐putamen. Moderate levels of [³H]‐spiperone binding were observed in control animals in the NAc, OT, SNc, and the lateral segment of globus pallidus (GPl). [³H]‐spiperone binding in the SNc and OT was partially decreased in MPTP‐treated animals. The changes in specific [³H]‐spiperone and [³H]‐SCH 23390 binding induced by MPTP‐treatment did not alter with post‐lesion survival times. These results demonstrate that MPTP treatment causes greater dopaminergic denervation of the caudate‐putamen than in NAc/OT. This resulted in an increase in postsynaptic D‐1 DA receptor sites in the caudate‐putamen but not in the NAc/OT. Also, there appeared to be loss of presynaptic D‐2 DA receptic sites in the SNc and OT. In the caudate‐putamen, the loss of presynaptic D‐2 DA receptor sites may have masked postsynaptic D‐2 DA receptor upregulation. © 1993 Wiley‐Liss, Inc.