Ando Kiyoshi, Maeda Jun, Inaji Motoki, Okauchi Takashi, Obayashi Shigeru, Higuchi Makoto, Suhara Tetsuya, Tanioka Yoshikuni
Department of Marmoset Research, Central Institute for Experimental Animals, 1430 Nogawa, Miyamaeku, Kawasaki 216-0001, Japan.
Psychopharmacology (Berl). 2008 Jan;195(4):509-16. doi: 10.1007/s00213-007-0929-2. Epub 2007 Sep 19.
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.
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).
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 [(11)C]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.
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.
尝试建立一种临床前方法，以1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的普通狨猴为研究对象，以l-司来吉兰（DEP）作为参比药物，评估帕金森病药物的行为保护作用。
15只狨猴连续3天每天皮下注射2mg/kg MPTP。在DEP3组中，每次MPTP给药前2小时对这些狨猴进行10mg/kg DEP的胃内给药，在DEP1组中仅在首次MPTP给药日进行预处理。作为对照，每次MPTP给药前给予蒸馏水（DW）（三组每组n = 5）。
在DW组中，MPTP给药后3周持续观察到每日活动计数减少和功能障碍评分增加。在DEP组中，MPTP给药后数天暂时观察到与DW组相似的水平变化，然后这些值恢复到MPTP给药前的水平。上述行为观察后进行的放射自显影结果表明，与另外制备的未用MPTP处理的狨猴（n = 5）的纹状体相比，DW组狨猴纹状体中[(11)C]PE2I（多巴胺转运体配体）的结合明显降低。DEP组的结合与未用MPTP处理的狨猴脑内的结合几乎相同。
目前使用在生活笼中连续记录狨猴活动以及使用多巴胺转运体配体进行放射自显影的临床前方法，可能对检测帕金森病药物的保护作用敏感。
