Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Providing reference data for efficacious preclinical evaluations

Kiyoshi Ando, Takashi Inoue, Keigo Hikishima, Yuji Komaki, Kenji Kawai, Ryo Inoue, Chiyoko Nishime, Eiko Nishinaka, Koji Urano, Hideyuki Okano

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Baseline locomotion and behavioral traits in the common marmoset Parkinson's disease model were examined to provide basic information for preclinical evaluations of medical treatments. A single regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine at a cumulative dose of 5 mg/kg as the free base over three consecutive days was administered subcutaneously to 10 marmosets. Data obtained from these marmosets were compared to pre-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine levels or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine free marmosets. After the single regimen, reduced daily locomotion, a measure of immobility (a primary sign of Parkinsonism), was observed for more than a year. A moving tremor was also observed by visual inspection during this period. When apomorphine (0.13 mg/kg, s.c.) was administered, either right or left circling behavior was observed in a cylindrical chamber in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets, suggestive of unequal neural damage between the two brain hemispheres to different extents. MRI revealed that T1 relaxation time in the right substantia nigra correlated with right circling in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets. Histology was supportive of dopaminergic neural loss in the striatum. These results increase our understanding of the utility and limitations of the Parkinson's disease model in marmosets with a single 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine regimen, and provide reference data for efficacious preclinical evaluations.

Original languageEnglish
Pages (from-to)45-60
Number of pages16
JournalBehavioural pharmacology
DOIs
Publication statusPublished - 2020 Feb 1

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • MRI
  • Parkinson's disease
  • circling
  • locomotor activity
  • marmoset

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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