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
| Autor: | Kiyoshi Ando, Chiyoko Nishime, Keigo Hikishima, Yuji Komaki, Takashi Inoue, Eiko Nishinaka, Kenji Kawai, Ryo Inoue, Koji Urano, Hideyuki Okano |
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| Rok vydání: | 2019 |
| Předmět: |
Parkinson's disease
Dopamine Physiology Striatum 03 medical and health sciences 0302 clinical medicine Parkinsonian Disorders biology.animal Tremor medicine Animals Pharmacology marmoset biology Behavior Animal business.industry Cumulative dose Parkinsonism Dopaminergic Marmoset Brain Callithrix Parkinson Disease Research Reports medicine.disease Corpus Striatum 030227 psychiatry Apomorphine Substantia Nigra Psychiatry and Mental health Regimen Disease Models Animal 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine circling ComputingMethodologies_DOCUMENTANDTEXTPROCESSING business locomotor activity 030217 neurology & neurosurgery Locomotion medicine.drug MRI |
| Zdroj: | Behavioural Pharmacology |
| ISSN: | 1473-5849 |
| Popis: | Supplemental Digital Content is available in the text. 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. |
| Databáze: | OpenAIRE |
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