The overall rod performance test in the MPTP-treated-mouse model of Parkinsonism

J Neurosci Methods. 1998 Sep 1;83(2):165-75. doi: 10.1016/s0165-0270(98)00078-8.

Abstract

We investigated the usefulness of the Overall Rotarod Performance (ORP) test for evaluating overall locomotory ability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected-mouse model of Parkinson's disease (PD). For this procedure, the mice are pretrained on the rotarod and then tested at a series of increasing speeds, recording the time that the animal remains on the rod at each speed; the overall rod performance (ORP) of each animal is then calculated as the area under the curve in a plot of time-on-the-rod against rotation speed. At 15-day intervals, C57BL/6 mice were injected (or sham-injected) with MPTP, with ORP testing 7-10 days after each injection. After the fourth injection (day 45), mice in the treated group showed clearly lower ORP than mice in the control group (70-90% reduction in ORP), and were thus considered effectively lesioned. Subsequently, we investigated the short-term effects of apomorphine and L-DOPA on ORP in MPTP-treated mice. Apomorphine (at 0.5 or 2.5 mg/kg) had no significant effect, while L-DOPA (at 80 but not at 40 mg/kg) caused almost complete short-term recovery of pretreatment ORP. By about 100 days after the last MPTP injection, MPTP-treated mice showed partial long-term recovery of ORP; at this stage the mice were killed for tyrosine hydroxylase (TH) immunohistochemistry studies. TH immunoreactivity in the striatum showed a strong positive correlation with ORP as tested on day 100. We conclude that the ORP test is useful for evaluating motor deficit in MPTP-treated mice, and the effects of subsequent treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
  • Animals
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Dopamine Agents*
  • Dopamine Agonists / pharmacology
  • Levodopa / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Neurons / enzymology
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / physiopathology*
  • Tyrosine 3-Monooxygenase / analysis

Substances

  • Dopamine Agents
  • Dopamine Agonists
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Apomorphine