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Current Topics in Pharmacology   Volumes    Volume 2 
Progressive biphasic damage to the nigrostriatal pathway induced by chronic MPTP treatment in baboons: A positron emission tomography study using 6- (18F) fluoro-L-Dopa
Maora Varastet, Philippe Hantraye, Michel Bottalender, Chantal Fuseau, Pierre Cesaro, Emmanuel Brouillet, Lorenz Schmid, Francoise Hinnen, Mariannick Mazière
Pages: 11 - 19
Number of pages: 9
Current Topics in Pharmacology
Volume 2 

Copyright © 1993 Research Trends. All rights reserved

Chronic exposure to MPTP induces in baboons a clinical syndrome and an uneven loss of midbrain dopaminergic neurons similar to those observed in idiopathic Parkinson’s disease (PD). The relationship between clinical evolution and progressive dysfunction of the nigrostriatal pathway was studied in vivo using positron emission tomography (PET) and 6-[18F]fluoro-L-DOPA ([18F]DOPA), a marker of the integrity of the dopamine nerve terminals. Four baboons received weekly intravenous MPTP injections over 17-21 months. An asymptomatic phase lasting 20-24 weeks was observed first, associated with a progressive but rapid decrease (>60%) in striatal [18F]DOPA uptake. In a second phase during which symptoms gradually appeared and increased in severity, the striatal uptake further decreased to 20% of control values. The caudate nucleus was consistently less affected than the putamen. This replicates the relative sparing of the caudate dopamine function observed in patients. When animals received daily MPTP injections prior to the chronic treatment, symptoms appeared shortly after the start of the chronic treatment and were accompanied by a rapid and severe (95%) decrease in striatal [18F]DOPA uptake, with no particular sparing of the caudate nucleus. These PET studies demonstrate that chronic MPTP injections better replicate the neurochemical and behavioural features of PD than do more acute intoxication regimens, by targeting preferentially the dopamine neurons projecting to the putamen.
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