Cardiac
sympathetic denervation occurs commonly in
Parkinson's disease. This study explored whether analogous
denervation occurs in primates with
Parkinsonism from systemic administration of
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP). 6-[18F]Fluorodopamine positron emission tomographic scanning and plasma levels of
catecholamines and their deaminated metabolites were used to assess sympathetic and adrenomedullary function in rhesus monkeys, in the untreated state (n = 3), 2 weeks after a series of four
MPTP injections, before establishment of
Parkinsonism (acute phase, n = 1); a month later, after four more
MPTP doses, associated with severe
Parkinsonism (subacute phase, n = 1); or more than 2 years from the last dose (remote phase, n = 3), with persistent severe
Parkinsonism. A positive control received i.v.
6-hydroxydopamine 1 week before 6-[18F]fluorodopamine scanning. Acute
MPTP treatment increased cardiac 6-[18F]fluorodopamine-derived radioactivity, whereas
6-hydroxydopamine markedly decreased cardiac radioactivity, despite similarly low plasma levels of
catecholamines and metabolites after either treatment. Subacutely, plasma
catecholamines remained decreased, but now with myocardial 6-[18F]fluorodopamine-derived radioactivity also decreased. Remotely,
MPTP-treated monkeys had lower plasma
catecholamines and higher myocardial 6-[18F]fluorodopamine-derived radioactivity than did untreated animals. The results indicate that in nonhuman primates, systemic
MPTP administration produces multiphasic effects on peripheral
catecholamine systems, with nearly complete recovery by 2 years.
MPTP- and 6-hydroxydopamine-induced changes differ markedly, probably from ganglionic or preganglionic neurotoxicity with the former and more severe cardiac sympathetic neurotoxicity with the latter. Because of multiphasic sympathetic and adrenomedullary effects, without cardioselective
sympathetic denervation at any time, the primate
MPTP model does not mimic the changes in peripheral
catecholamine systems that characterize the human disease.