Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmosets

Kiyoshi Ando, Jun Maeda, Motoki Inaji, Takashi Okauchi, Shigeru Obayashi, Makoto Higuchi, Tetsuya Suhara, Yoshikuni Tanioka

研究成果: ジャーナルへの寄稿学術論文査読

35 被引用数 (Scopus)

抄録

Objective: Establishment of preclinical method evaluating behavioral protective actions of drugs for Parkinson's disease was attempted using l-deprenyl (DEP) as a reference drug in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated common marmosets. Materials and methods: Fifteen marmosets received MPTP at 2 mg/kg, subcutaneously (s.c.) per day for three consecutive days. To these marmosets, intragastric (i.g.) administration of DEP at 10 mg/kg was pretreated 2 h before each MPTP administration in DEP3 group and pretreated only in the first MPTP administration day in DEP1 group. As a control, distilled water (DW) was pretreated before each MPTP administration (n=5 for each of three groups). Results: In DW group, decreased daily activity counts and increased dysfunction scores were persistently observed for 3 weeks after MPTP. In DEP groups, the similar changes of both levels to those in DW group were temporally observed after MPTP for several days and then the values recovered to the pre-MPTP levels. The results of autoradiography performed after above behavioral observations indicated that markedly lower bindings of [ 11C]PE2I (ligand for dopamine transporters) were observed at the striatum of DW group marmoset as compared with the striatum of additionally prepared MPTP-free marmoset (n=5). The bindings in DEP groups were almost the same as in the MPTP-free marmoset brains. Conclusion: The present preclinical methods using continuous recording of activity of marmosets in their living cages and autoradiography using dopamine transporter ligand might be sensitive for detecting protective actions of drugs for Parkinson's disease.

本文言語英語
ページ(範囲)509-516
ページ数8
ジャーナルPsychopharmacology
195
4
DOI
出版ステータス出版済み - 01-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学

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