THE MPTP-INDUCED PARKINSONIAN-SYNDROME IN THE GOLDFISH IS ASSOCIATED WITH MAJOR CELL DESTRUCTION IN THE FOREBRAIN AND SUBTLE CHANGES IN THEOPTIC TECTUM

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce a parkinsonian syndrome in humans and nonhuman primates, which is susceptible to treatment and prevention by drugs such as L-DOPA an d L-deprenyl, Recently, we have reported that MPTP can also cause a pa rkinsonian syndrome in the common goldfish, which appears to faithfull y mirror the neurochemical and behavioral aspects of the action of MPT P in the higher vertebrates. In addition, we recently identified the l ikely teleost equivalent of the substantia nigra in the goldfish foreb rain, the ''nucleus pars medialis,'' on the basis of its destruction b y MPTP and selective protection by the MAO-B blocker L-deprenyl. In th e present work we substantiate this conclusion by examining tissue des truction in the goldfish forebrain at increasing MPTP concentrations, up to the the LD(50) Of 200 mg/kg, In addition, we show that at the hi ghest MPTP dose subtle changes also occur with low frequency in nondop aminergic cells in the optic tectum, and in ependymal cells lining the midbrain ventricle, The effects on ependymal cells are similar to tho se previously noted in the forebrain. We conclude that the goldfish mo del continues to faithfully mimic the histologic pattern of parkinsoni an tissue destruction engendered by MPTP in primate models. (C) 1996 A cademic Press, Inc.