STRIATAL DOPAMINERGIC MARKERS, NIGRAL VOLUME, AND ROTATIONAL BEHAVIORFOLLOWING IRON INFUSION INTO THE RAT SUBSTANTIA-NIGRA

Excess iron (Fe) within the substantia nigra zona compacta (SNc) has b een implicated in the pathogenesis of Parkinson's disease (PD). We rec ently reported that intranigral Fe infusion into the rat substantia ni gra (SN) induces dose-dependent SN neurodegeneration and associated re ductions in striatal dopaminergic (DA) markers. The objective of the p resent study was to determine whether infused Fe is capable of inducin g persistent/progressive neurodegenerative changes relevant to PD. Fol lowing unilateral infusions of vehicle, 1.25 or 2.10 nmol Fe into the rat SN, SNc neuronal loss, SN volume, striatal neurochemical markers, and apomorphine-induced rotational behavior were assessed at 2, 4, and 6 months. Semiquantitative analysis of thionine-stained SNc neurons d emonstrated an initial modest neuronal loss which remained stable thro ugh 6 months postinfusion. Fe-induced SN atrophy was dose-dependent an d progressive through 6 months. Striatal DA and homovanillic acid leve ls were progressively decreased at least through 4 months following 1. 25 nmol Fe infusion; both doses of Fe induced significant reductions o f both DA markers at 4 months with no recovery evident through 6 month s. Apomorphine-induced rotational behavior progressively increased for both Fe infusion groups through the 6 months of testing. These data i ndicate that a single exposure of the SN to a modest amount of Fe can induce persistent/progressive changes occurring through a number of mo nths postinfusion and further establishes intranigral Fe infusion as a n animal model for PD. (C) 1994 Academic Press, Inc.