Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: histological, neurochemical, motor and memory alterations

J Neurosci Methods. 2005 Oct 15;148(1):78-87. doi: 10.1016/j.jneumeth.2005.04.005. Epub 2005 Jun 6.


This study compares histological, neurochemical, behavioral, motor and cognitive alterations as well as mortality of two models of Parkinson's disease in which 100 microg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 microg 6-hydroxydopamine (6-OHDA) was bilaterally infused into the central region of the substantia nigra, compact part, of adult male Wistar rats. Both neurotoxins caused a significant loss of nigral tyrosine hydroxylase-immunostained cells and striatal dopamine depletion, but 6-OHDA caused more widespread and intense cell loss, more intense body weight loss and more mortality than MPTP. Both 6-OHDA- and MPTP-lesioned rats presented similar deficits in performing a working memory and a cued version of the Morris water maze task and few exploratory/motor alterations in the open field and catalepsy tests. However, rats presented a significant and transitory increase in locomotor activity after the MPTP lesion and a hypolocomotor behavior tended to be present after the 6-OHDA lesion. The picture of mild motor effects and robust impairment of habit learning and spatial working memory observed in MPTP-lesioned rats models the early phase of Parkinson's disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
  • Adrenergic Agents
  • Analysis of Variance
  • Animals
  • Brain Chemistry / drug effects*
  • Disease Models, Animal
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Oxidopamine*
  • Parkinsonian Disorders* / chemically induced
  • Parkinsonian Disorders* / pathology
  • Parkinsonian Disorders* / physiopathology
  • Rats
  • Rats, Wistar
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiopathology
  • Time Factors


  • Adrenergic Agents
  • Oxidopamine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine