Clonidine suppresses 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced reductions of striatal dopamine and tyrosine hydroxylase activity in mice

F. Fornai, M. G. Alessandri, F. Fascetti, F. Vaglini, G. U. Corsini

Research output: Contribution to journalArticle

Abstract

Recent findings have shown that excitatory amino acid may be involved in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. At the same time, evidence is accumulating that the endogenous noradrenergic system plays a protective role in MPTP-induced striatal dopamine (DA) depletion and nigral dopaminergic cell death. Recently, α2-adrenoceptors located on glutamatergic axons have been shown to inhibit glutamate overflow. In this study, we evaluated the effects of an α2-agonist (clonidine) and an α2- antagonist (yohimbine) on MPTP-induced striatal DA depletion and tyrosine hydroxylase activity reduction. We show that clonidine is able to prevent the neurotoxicity of MPTP in mice. To exert this effect, clonidine (0.5 mg/kg) must be administered at least twice (30 min before and 30 min after MPTP). Administration of another α2-agonist (detomidine, 0.3 mg/kg) attenuated the neurotoxicity induced by MPTP. We provide evidence that the protective effect obtained with clonidine was not due to decreased striatal content of 1- methyl-4-phenylpyridinium (MPP+). We also show that yohimbine, which is a classic α2-adrenoceptor antagonist with low affinity for imidazoline receptors, produced by itself an enhancement of MPTP toxicity and was able to block the protective effect of clonidine. These data raise the possibility that α2-adrenoceptor may modulate the susceptibility of the nigrostriatal dopaminergic pathway to neurotoxicity.

Original languageEnglish
Pages (from-to)704-709
Number of pages6
JournalJournal of Neurochemistry
Volume65
Issue number2
Publication statusPublished - 1995

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine
  • Clonidine
  • Detomidine
  • Parkinsonism
  • Yohimbine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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