In vivo PET studies of the dopamine D2 receptors in rhesus monkeys with long-term MPTP-induced parkinsonism

Studies of dopamine (DA) receptor binding in early parkinsonian patients, o r in models of Parkinson's disease, have revealed a supersensitivity of the DB-like receptor subtype as compared to age-matched controls. The lack of upregulation in advanced patients is often attributed to the effects of pro longed antiparkinsonian therapy, but the impact of therapy vs. intrinsic me chanisms in untreated patients or animals with long-term lesions of the DA nigrostriatal pathway has been difficult to address. We studied, in vivo, b y PET using the DA D2 receptor ligand raclopride, the status of the DA rece ptors in normal rhesus monkeys and those with acute (3 months) or long-term (10 years) MPTP-induced nigrostriatal lesions. Compared to age-matched con trols, there was no change in raclopride binding in MPTP-treated animals wi thout parkinsonian symptoms. There was a significant increase in raclopride binding in the putamen (but not caudate nucleus) of all the animals displa ying rigidity, hypo- and bradykinesia. This increase was greater in the ani mals with acute lesions (32%) than with established, long-term lesions (18% ). There was no correlation between the postmortem striatal DA concentratio ns and in vivo raclopride binding but there was a correlation between PET r aclopride binding and [H-3]radopride binding in vitro. Complex changes in D 2 receptor binding occur in various stages of parkinsonism. Antiparkinsonia n therapy is unlikely to be solely responsible for the lack of upregulation found in advanced parkinsonian patients but may be a contributing factor. (C) 2000 Wiley-Liss, Inc.