Parkinsonism in monkeys produced by chronic administration of an endogenous substance of the brain, tetrahydroisoquinoline: the behavioral and biochemical changes.
We have examined the effect of chronic administration of a probable endogenous dopaminergic neurotoxin, tetrahydroisoquinoline (TIQ, 20 mg/kg per day, s.c. for up to 104 days), on squirrel monkeys. Chronically administered TIQ produced motor symptoms similar to parkinsonism in squirrel monkeys even after 7 days' discontinuation of TIQ and the symptomes were alleviated remarkably by levodopa treatment. Biochemical analysis of the brains of TIQ-treated monkeys revealed significant decrease in dopamine (DA) and total biopterin (BP) concentrations, and tyrosine hydroxylase (TH) activity in the substantia nigra, and these biochemical changes were not reversed by 7 days following the termination of chronic administration of TIQ. TIQ was identified in the brain (caudate-putamen) of saline-injected control monkeys by gas chromatography-mass spectrometry. The endogenous levels of TIQ in the caudate-putamen was about 0.15 micrograms/g, and increased up to 3-4 micrograms/g, 1 day as well as 7 days following termination of TIQ administration.
Yoshida
M
M
Department of Neurology, Jichi Medical School, Tochigi-ken, Japan.
Niwa
T
T
Nagatsu
T
T
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001522:Behavior, Animal; D001545:Benserazide / Q000494:pharmacology; D001708:Biopterins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D012453:Saimiri; D013997:Time Factors; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001708:Biopterins; D007980:Levodopa; D001545:Benserazide; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine