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 we re studied pharmacologically by a intracerebral injection of paraquat. The neurochemical, morphological, and behavioral changes observed aft er a unilateral intranigral injection of paraquat (1-5 mu g) were as f ollows: (1) neurochemically, paraquat caused dose-dependent depletion of dopamine in the ipsilateral striatum starting 2 weeks after treatme nt; this effect was longlasting and irreversible. The ipsilateral stri atal dopamine level in animals treated with 3 mu g paraquat was even d ecreased by 91.5%. (2) Morphologically, 2 mu g of paraquat produced ma rked loss of Nissl substances and prominent glial reaction in the subs tantia 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 adm inistration (0.5 mg/kg, sc). This effect was dose-dependent and lasted for the entire 16-week experimental period. Taken together, these dat a indicate that intranigrally injected paraquat may possess marked neu rotoxicity and induce degeneration of the rat nigrostriatal dopaminerg ic system. (C) 1996 Academic Press, Inc.