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Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP+

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Summary

Unilateral intranigral administration of the oxidative metabolites of 1-methyl-4-pheny1-1,2,3,6-tetrahydropyridine (MPTP), 1-methyi-4-phenyl-dihydropyridine (MPDP+) or l-methyl-4-phenylpyridine (MPP+) produced dose-dependently a depletion of dopamine in the ipsilateral striatum of rats two weeks following treatment.d- Amphetamine and apomorphine induced circling toward the lesioned side in these unilaterally treated animals. No contralateral circling behavior was observed after challenging with apomorphine. This dopamine lesioning effect of MPP+ was not blocked by pretreatment of animals with a dopamine uptake blocker, GBR 12909.

Furthermore, MPP+ increased the45Ca accumulation into cells at the site of injection and produced “nonspecific” cell membrane and/or cytotoxic damage seen by histological procedures. These results indicate that MPDP+ and MPP+ produced localized cytotoxic damage to nigrostriatal neurons, caused a decrease in striatal dopamine, and disrupted the nigrostriatal system's functioning following intranigral administration to rats. It is postulated that the cationic surfactant properties of MPDP+ and MPP+ might contribute to its neurotoxic effects.

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Author notes

  1. C. C. Chiueh

    Present address: National Institute of Mental Health, USA

Authors and Affiliations

  1. Food and Drug Administration, USA

    C. J. Sun

  2. National Institute of Mental Health, USA

    J. N. Johannessen, I. Namura & W. Singhaniyom

  3. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA

    W. Gessner & A. Brossi

Authors
  1. C. J. Sun
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  2. J. N. Johannessen
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  3. W. Gessner
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  4. I. Namura
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  5. W. Singhaniyom
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  6. A. Brossi
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  7. C. C. Chiueh
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Sun, C.J., Johannessen, J.N., Gessner, W. et al. Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP+ . J. Neural Transmission 74, 75–86 (1988). https://doi.org/10.1007/BF01245141

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