Extensive loss of brain dopamine and serotonin induced by chronic administration of MPTP in the marmoset.
Common marmosets were given a subcutaneous injection of MPTP (1.25-2.5 mg/kg twice a week) for 5 or 10 consecutive months and were sacrificed after a survival time of 6 months or 15 days, respectively. The parkinsonian symptoms were not very marked at the time of sacrifice but there was a strong decrease of dopamine and, to a lesser extent, of its metabolites in the striatum and in some extrastriatal regions. There was also a profound loss of serotonin in the striatum and in all of the extrastriatal regions analyzed, which was still highly significant 6 months after discontinuation of MPTP treatment. The results suggest that the selected dosage schedule produces a widespread and lasting neuronal degeneration closely resembling the neurochemical pathology of Parkinson's disease.
Pérez-Otaño
I
I
Department of Pharmacology, Clínica Universitaria, University of Navarra Medical School, Pamplona, Spain.
Herrero
M T
MT
Oset
C
C
De Ceballos
M L
ML
Luquin
M R
MR
Obeso
J A
JA
Del Río
J
J
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002144:Callithrix; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D009928:Organ Specificity; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid