Open AccessMeasurement 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
Author(s) -
Kiyoshi Ando,
Takashi Inoue,
Keigo Hikishima,
Yuji Komaki,
Kenji Kawai,
Rikako Inoue,
Chiyoko Nishime,
Eiko Nishinaka,
Koji Urano,
Hideyuki Okano
Publication year - 2020
Publication title -
behavioural pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 80
eISSN - 1473-5849
pISSN - 0955-8810
DOI - 10.1097/fbp.0000000000000509
Subject(s) - marmoset , mptp , parkinson's disease , substantia nigra , parkinsonism , regimen , striatum , medicine , dopaminergic , pars compacta , callithrix , psychology , neuroscience , disease , dopamine , biology , paleontology
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.