Melatonin treatment potentiates neurodegeneration in a rat rotenone Parkinson's disease model

J Neurosci Res. 2010 Feb 1;88(2):420-7. doi: 10.1002/jnr.22201.


Parkinson's disease (PD) is characterized pathologically by progressive neurodegeneration of the nigrostriatal dopamine (DA) system. Currently, the cause of the disease is unknown, except for a small percentage of familial cases (<10% of total). The rat rotenone model reproduces many of the pathological features of the human disease, including apomorphine-responsive behavioral deficits, DA depletion, loss of striatal DA terminals and nigral dopaminergic neurons, and alpha-synuclein/polyubiquitin-positive cytoplasmic inclusions reminiscent of Lewy bodies. Therefore, this model is well-suited to examine potential neuroprotective agents. Melatonin is produced mainly by the pineal gland and is known primarily for regulating circadian rhythms. It also has potent free radical scavenging and antiinflammatory properties. Melatonin has been reported to be neuroprotective in the 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. However, there are conflicting reports suggesting that melatonin does not provide neuroprotection in these models. Melatonin elicits significant functional changes in the nigrostriatal DA system that may affect 6-OHDA and MPTP entry into cells. Therefore, rotenone is an ideal model for assessing protection, because it does not rely on the dopamine transporter uptake to exert neurotoxicity. In this study, the neuroprotective potential of melatonin in the rotenone PD model was assessed. Melatonin potentiated striatal catecholamine depletion, striatal terminal loss, and nigral DA cell loss. Indeed, melatonin alone elicited alterations in striatal catecholamine content. Our findings indicate that melatonin is not neuroprotective in the rotenone model of PD and may exacerbate neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Count
  • Cell Death / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Melatonin / adverse effects*
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents / adverse effects*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / physiopathology*
  • Random Allocation
  • Rats
  • Rats, Inbred Lew
  • Rotenone
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology
  • Survival Analysis
  • Tyrosine 3-Monooxygenase / metabolism


  • Neuroprotective Agents
  • Rotenone
  • Tyrosine 3-Monooxygenase
  • Melatonin
  • Dopamine