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Suppression of MPTP-induced dopaminergic neurotoxicity in mice by nomifensine andl-DOPA

Authors
Journal
Brain Research
0006-8993
Publisher
Elsevier
Publication Date
Volume
342
Issue
2
Identifiers
DOI: 10.1016/0006-8993(85)91146-1
Keywords
  • N-Methyl-4-Phenyl-1
  • 2
  • 5
  • 6-Tetrahydropyridine (Mptp)
  • Neurotoxicity
  • Nigrostriatal Dopaminergic Neuron
  • Nomifensine
  • L-Dihydroxyphenylalanine (L-Dopa)
  • Apomorphine
  • Bromocriptine
  • Haloperidol
Disciplines
  • Biology
  • Pharmacology

Abstract

Abstract To examine effects of various pharmacological manipulations of dopamine (DA) metabolism on DA neurotoxicity of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), C57 black mice were injected with MPTP (30 mg/kg s.c., once daily for two days) alone or in combination with apomorphine, bromocriptine, haloperidol, l-DOPA or nomifensine. MPTP markedly decreased neostriatal DA concentrations at 2, 10, 20 and 30 days post-treatment indicating persistent degeneration of nigrostriatal DA neurons. Suppression or acceleration of DA turnover rates by the DA agonists apomorphine and bromocriptine or by the DA antagonist haloperidol, respectively, did not affect MPTP toxicity. MPTP-induced neostriatal DA depletions were markedly suppressed by nomifensine, a DA reuptake inhibitor, and attenuated by exogenous l-DOPA. MPTP may be a substrate for the DA reuptake system and its specific transport into nigrostriatal terminals may be an important factor for its selective neurotoxicity.

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