Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents

J Pineal Res. 2009 Nov;47(4):293-300. doi: 10.1111/j.1600-079X.2009.00713.x. Epub 2009 Oct 1.


We tested the hypothesis that melatonin regulates formation of 6-hydroxydopamine (6-OHDA) in the brain and thereby protects animals from dopaminergic neurotoxicity and the development of parkinsonism in animals. Employing a ferrous-ascorbate-dopamine (FAD) hydroxyl radical ((*)OH) generating system, in the present study we demonstrate a dose-dependent attenuation of 6-OHDA generation by melatonin in vitro. Intra-median forebrain bundle infusion of FAD caused significant depletion of striatal dopamine (DA), which was blocked by melatonin. Per-oral administration of l-3,4-dihydroxyphenylalanine (L-DOPA) for 7 days caused a dose-dependent increase in the formation of 6-OHDA in the mouse striatum, which was increased synergistically by the systemic administration of the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the 7th day of L-DOPA treatment. Melatonin treatment significantly attenuated both the L-DOPA and MPTP-induced increases in the levels of striatal 6-OHDA, and protected against striatal DA depletion caused by the neurotoxin. These observations suggest a novel mode of melatonin-induced dopaminergic neuroprotection in two models of Parkinson's disease, and suggest the possible therapeutic use of this well-known antioxidant indoleamine neurohormone in parkinsonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Ascorbic Acid / pharmacology
  • Brain / drug effects*
  • Brain / metabolism*
  • Central Nervous System Depressants / pharmacology*
  • Chromatography, High Pressure Liquid
  • Dopamine / pharmacology
  • Dopamine Agents / pharmacology
  • Ferrous Compounds / pharmacology
  • Levodopa / pharmacology
  • Male
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Oxidopamine / metabolism*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / prevention & control*


  • Central Nervous System Depressants
  • Dopamine Agents
  • Ferrous Compounds
  • iron(II)-ascorbic acid complex
  • Levodopa
  • Oxidopamine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Melatonin
  • Ascorbic Acid
  • Dopamine