ELECTRON-MICROSCOPIC EVIDENCE FOR NEUROTOXICITY IN THE BASAL GANGLIA

The dopaminergic projection from the substantia nigra to the neostriat um is vulnerable to several neurotoxins including 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP), amphetamine, and 5-hydroxydopamine. W e have treated rats or mice with these agents and examined various reg ions of their brains with a combination of Fink-Heimer, immunohistoche mical, serial-section electron microscopic, and three-dimensional reco nstruction methods. In addition to degenerating or swollen axons, we f ound darkened glial processes and some damage to postspnaptic cells an d dendrites. The particular effects observed critically depend on expe rimental variables such as dose, time, species and strain and raise qu estions about the correlation of light and electron microscopic result s. These studies provide the basis for a discussion of the advantages and disadvantages of an ultrastructural examination of the effects of neurotoxins.