Neuropathological lesions after microinfusion of paraquat and MPP+ into different areas of the rat brain
Iannone, M.; Calò, M.; Rispoli, V.; Sancesario, G.; Nisticò, G.
Acta Neurologica 10(6): 313-321
1988
ISSN/ISBN: 0001-6276 PMID: 3265850 Document Number: 4371
The present experiments were aimed to better characterize the neurotoxicological profile of paraquat and MPP+, two compounds sharing a similar chemical structure. Paraquat is a widely used herbicide, whereas MPP+ is the active metabolite of MPTP, a compound selectively neurotoxic for the dopaminergic nigro-striatal pathway leading to a parkinson-like disease in several animal species and man. In rats with cannulas chronically implanted by means of a stereotaxic instrument into various areas of the brain, paraquat and MPP+ microinfused into the s. nigra (pars compacta) produced dose-dependent degenerative lesions culminating into death of nigral neurons. In addition, a low dose (1.6 nmol) of both paraquat and MPP+ after intranigral microinfusion produced 5 and 8 days later a selective degeneration of hippocampal CA3 neurons. As far as behavioural and ECoG changes are concerned, paraquat at higher doses produced contralateral head-neck deviation, circling, jumping, wet-dog syndrome and motor and ECooG epileptic disorders. Neuropathological lesions and behavioural and motor alterations induced by MPP+ after microinfusion into the same sites were less intense but similar to those evoked by equimolar dose of paraquat. However, neuropathological lesions and motor alterations induced by both neurotoxins were not specific for the nigrostriatal dopaminergic system since paraquat and MPP+ given into other nuclei containing non-dopaminergic cell bodies, i.e. locus coeruleus and raphe nuclei, produced locally neuropathological lesions similar to those observed in the s. nigra after intranigral infusion.
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