Effects of paraquat on the substantia nigra of the Wistar rats: Neurochemical, histological, and behavioral studies

Effects of paraquat on the substantia nigra of the male Wistar rats were studied pharmacologically by a intracerebral injection of paraquat. The neurochemical, morphological, and behavioral changes observed after a unilateral intranigral injection of paraquat (1-5 mu g) were as follows: (1) neurochemically, paraquat caused dose-dependent depletion of dopamine in the ipsilateral striatum starting 2 weeks after treatment; this effect was longlasting and irreversible. The ipsilateral striatal dopamine level in animals treated with 3 mu g paraquat was even decreased by 91.5%. (2) Morphologically, 2 mu g of paraquat produced marked loss of Nissl substances and prominent glial reaction in the substantia nigra, while 3 mu g of paraquat caused a severe loss of neurons. (3) Behaviorally, paraquat caused a vigorous rotational behavior in rats contralateral to the lesioned side in response to apomorphine administration (0.5 mg/kg, sc). This effect was dose-dependent and lasted for the entire 16-week experimental period. Taken together, these data indicate that intranigrally injected paraquat may possess marked neurotoxicity and induce degeneration of the rat nigrostriatal dopaminergic system. (C) 1996 Academic Press, Inc.