Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with 11C-CFT

Exp Neurol. 1994 Apr;126(2):305-9. doi: 10.1006/exnr.1994.1069.

Abstract

We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Carbon Radioisotopes*
  • Caudate Nucleus / diagnostic imaging*
  • Caudate Nucleus / pathology
  • Caudate Nucleus / physiopathology
  • Cocaine / analogs & derivatives*
  • Cocaine / metabolism
  • Cocaine / pharmacokinetics
  • Dopamine / analysis
  • Dopamine / metabolism*
  • Motor Activity*
  • Nerve Endings / diagnostic imaging
  • Nerve Endings / pathology
  • Parkinson Disease, Secondary / diagnostic imaging*
  • Parkinson Disease, Secondary / pathology
  • Parkinson Disease, Secondary / physiopathology
  • Putamen / diagnostic imaging*
  • Putamen / pathology
  • Putamen / physiopathology
  • Tomography, Emission-Computed / methods

Substances

  • Carbon Radioisotopes
  • (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
  • Dopamine