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.