Objective and quantitative evaluation of motor function in a monkey model of Parkinson's disease

J Neurosci Methods. 2010 Jul 15;190(2):198-204. doi: 10.1016/j.jneumeth.2010.05.009. Epub 2010 May 19.

Abstract

Monkeys treated with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) are currently the best animal model for Parkinson's disease (PD) and have been widely used for physiological and pharmacological investigations. However, objective and quantitative assessments have not been established for grading their motor behaviors. In order to develop a method for an unbiased evaluation, we performed a video-based assessment, used qualitative rating scales, and carried out an in vivo investigation of dopamine (DA) transporter binding in systemically MPTP-treated monkeys. The video-based analysis of spontaneous movement clearly demonstrated a significant correlation with the qualitative rating score. The assessment of DA transporter (DAT) function by [(11)C]-CFT-PET showed that, when compared with normal animals, the MPTP-treated animals exhibited decreased CFT binding in the bilateral striatum, particularly in the dorsal part in the putamen and caudate. Among the MPTP-treated monkeys, an unbiased PET analysis revealed a significant correlation between CFT binding in the midbrain and qualitative rating scores or the amount of spontaneous movements. These results indicate that a video-based analysis can be a reliable tool for an objective and quantitative evaluation of motor dysfunction of MPTP-treated monkeys, and furthermore, that DAT function in the midbrain may also be important for the evaluation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain Mapping
  • Carbon Radioisotopes
  • Cocaine / analogs & derivatives
  • Disease Models, Animal
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dyskinesia, Drug-Induced / diagnosis*
  • Dyskinesia, Drug-Induced / metabolism
  • Dyskinesia, Drug-Induced / physiopathology
  • Macaca fascicularis
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / diagnosis*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / physiopathology
  • Positron-Emission Tomography
  • Severity of Illness Index
  • Video Recording

Substances

  • Carbon Radioisotopes
  • Dopamine Plasma Membrane Transport Proteins
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Cocaine