MPTP‐Induced Models of Parkinson's Disease in Mice and Non‐Human Primates

Naomi P. Visanji1, Jonathan M. Brotchie2

1 Toronto Western Research Institute, Toronto, Ontario, 2 Toronto Western Research Institute and Atuka Ltd., Toronto, Ontario
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.42
DOI:  10.1002/0471141755.ph0542s29
Online Posting Date:  July, 2005
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Abstract

The pro‐toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is widely used to create animal models of Parkinson's disease. This unit describes protocols for the production of stable and substantial lesions in the dopaminergic nigrostriatal pathway of mice and non‐human primates. The models can be employed for assessing the neural mechanisms underlying the development of Parkinson's disease and for screening potential therapies for the treatment of this condition.

Keywords: MPTP; Parkinson's disease; primate; mouse; levodopa‐induced dyskinesia

     
 
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Table of Contents

  • Basic Protocol 1: MPTP‐Induced Dopaminergic Lesions in Mice
  • Basic Protocol 2: Stable Dopaminergic Lesioning and Parkinsonism in Marmosets
  • Basic Protocol 3: Assessment of Marmosets Rendered Parkinsonian by Administration of MPTP
  • Alternate Protocol 1: Induction of Levodopa‐Induced Dyskinesia in the Marmoset Model of Parkinson's Disease
  • Support Protocol 1: Assessment of Dyskinesia Psychomimetic Behaviors for Behavioral Pharmacology Experiments
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: MPTP‐Induced Dopaminergic Lesions in Mice

  Materials
  • C57BL/6 male mice (25 to 30 g, 8 weeks old; Harlan)
  • Standard rodent diet
  • MPTP hydrochloride (Sigma)
  • 0.9% sterile saline
  • Test compound(s)
  • Reference compound (e.g., 10 mg/kg selegiline, an MAO‐B inhibitor; Sigma)
  • Rodent cages
  • 1‐ml syringes
  • 21‐ and 23‐G needles
  • Parafilm
  • Transparent plastic container to store MPTP‐filled syringes

Basic Protocol 2: Stable Dopaminergic Lesioning and Parkinsonism in Marmosets

  Materials
  • Adult common marmosets (Callithrix jaccus), 300 to 400 g (Harlan)
  • Teklad Global 20% protein primate diet 2050 (Harlan Teklad)
  • MPTP hydrochloride (Sigma)
  • 0.9% sterile saline
  • Test compound
  • Reference compound (e.g., L‐DOPA, 10 to 20 mg/kg)
  • 1‐ml syringes
  • 21‐ and 23‐G needles
  • Parafilm
  • Transparent plastic container to store MPTP‐filled syringes
NOTE: The room in which the marmosets are housed should be designated for the use of MPTP (see ).

Basic Protocol 3: Assessment of Marmosets Rendered Parkinsonian by Administration of MPTP

  Materials
  • Adult common marmosets (Callithrix jaccus), 300 to 400 g (Harlan)
  • Marmoset food (sliced banana, apples, and grapes)
  • Wire observation cages (0.8 × 0.8 × 0.7–m) with a Perspex sliding front (Harkes Industries) with a single branch situated at a diagonal slant across the center of the cage from the bottom left‐hand corner at the cage front to the top right‐hand corner at the rear of the cage
  • Video camera, video cassette, and tripod, or DVD recorder and DVDs
  • Infrared activity monitor and computer with appropriate data‐logging software, optional
  • Additional reagents and equipment for MPTP treatment (see protocol 2)
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Figures

Videos

Literature Cited

Literature Cited
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