Mori Atsushi, Ohashi Satoshi, Nakai Masami, Moriizumi Tetsuji, Mitsumoto Yasuhide
Research Unit for Neurological Diseases, Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima-city, Tokushima 771-0192, Japan.
Neurosci Res. 2005 Mar;51(3):265-74. doi: 10.1016/j.neures.2004.11.008. Epub 2005 Jan 8.
Contradictory data on behavioral changes in MPTP-treated C57BL/6 mice have been reported, even though the toxin-treated mice have been widely used for non-clinical studies as an in vivo model of Parkinson's disease (PD). We found that the duration of immobility in the tail suspension test (TST) was significantly increased in MPTP-treated C57BL/6 mice as compared with control mice without a significant change in the locomotor activity (LA). Dopamine (DA) contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased in the toxin-treated mice. These behavioral and neurobiochemical changes were almost completely inhibited by a pretreatment with deprenyl, a monoamine oxidase-B inhibitor. The stimulation of dopaminergic neurotransmission induced by L-dopa or a dopamine D2 receptor agonist ameliorated the increase in immobility time. Threshold level of striatal DA that produced the increase in immobility time in MPTP-treated mice was estimated to be between 11 and 27% of control level. We concluded that the increase in immobility time in the TST was induced by the nigrostriatal dopaminergic degeneration and was thought to be a consequence of motor dysfunction in this mouse model of PD.
尽管用毒素处理过的小鼠作为帕金森病（PD）的体内模型已被广泛用于非临床研究，但关于MPTP处理的C57BL/6小鼠行为变化的矛盾数据已有报道。我们发现，与对照小鼠相比，MPTP处理的C57BL/6小鼠在悬尾试验（TST）中的不动时间显著增加，而运动活性（LA）没有显著变化。毒素处理的小鼠纹状体中的多巴胺（DA）含量以及酪氨酸羟化酶和多巴胺转运体的蛋白水平显著降低。用单胺氧化酶B抑制剂司来吉兰预处理几乎完全抑制了这些行为和神经生化变化。左旋多巴或多巴胺D2受体激动剂诱导的多巴胺能神经传递刺激改善了不动时间的增加。估计MPTP处理的小鼠中导致不动时间增加的纹状体DA阈值水平在对照水平的11%至27%之间。我们得出结论，TST中不动时间的增加是由黑质纹状体多巴胺能变性诱导的，并且被认为是该PD小鼠模型中运动功能障碍的结果。
