Chronic administration of pharmacological levels of melatonin does not ameliorate the MPTP-induced degeneration of the nigrostriatal pathway

William W. Morgan, James F Nelson

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

An extensive literature suggests that melatonin may protect from the degenerative effects of central neurotoxins by acting as a free radical scavenger. The purpose of this study was to determine if melatonin would protect male C57BL6 mice from the toxicity of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to nigral dopamine (DA) neurons. Melatonin was initially dissolved in dimethyl sulfoxide (DMSO), diluted to 16 μg/ml and then provided in the drinking water for 4 weeks. Control mice drank the same final concentration of the DMSO diluent. One week before the termination of the experiment, randomly selected mice from the melatonin-treated and the DMSO-treated groups received two, three or four doses of 2.5 mg/kg MPTP free base administered subcutaneously at 2-h intervals. Additional DMSO-treated and melatonin-treated mice did not receive MPTP. Following tissue collection, melatonin concentration was measured in blood plasma collected from each animal and found to be 20-fold higher in melatonin-treated compared to DMSO-treated mice. Tyrosine hydroxylase (TH) activity and the levels of DA and dihydroxyphenylacetic acid (DOPAC) were not different in striata collected from melatonin-treated versus DMSO-treated mice which did not receive MPTP. Treatment with MPTP significantly reduced striatal TH activity, DA and DOPAC, but there were no significant differences in the reductions in any of these parameters observed in the melatonin-treated versus the DMSO-treated control mice that received the same total dosage of MPTP. These results show that the long-term administration of a high pharmacological dose of melatonin was ineffective in protecting nigral dopaminergic neurons from the neurotoxic effects of MPTP.

Original languageEnglish (US)
Pages (from-to)115-121
Number of pages7
JournalBrain Research
Volume921
Issue number1-2
DOIs
StatePublished - Dec 7 2001

Fingerprint

Melatonin
Dimethyl Sulfoxide
Pharmacology
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Substantia Nigra
Dopamine
4-phenyl-1,2,3,6-tetrahydropyridine
Corpus Striatum
Free Radical Scavengers
Acids
Neurotoxins
Drinking Water

Keywords

  • Aging
  • Dopamine
  • Melatonin
  • MPTP
  • Oxidative damage
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chronic administration of pharmacological levels of melatonin does not ameliorate the MPTP-induced degeneration of the nigrostriatal pathway. / Morgan, William W.; Nelson, James F.

In: Brain Research, Vol. 921, No. 1-2, 07.12.2001, p. 115-121.

Research output: Contribution to journalArticle

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