Niimi Kimie, Takahashi Eiki, Itakura Chitoshi
Brain Science and Life Technology Research Foundation, 1-28-12 Narimasu, Itabashi, Tokyo 175-0094, Japan.
Physiol Behav. 2009 Mar 2;96(3):464-9. doi: 10.1016/j.physbeh.2008.11.012. Epub 2008 Nov 27.
The motor function of senescence-accelerated mouse prone 6 (SAMP6) was evaluated with a battery of behavioral tests: locomotor activity test, traction test, wire hanging test, and rotating rod test. SAMP6 exhibited increased locomotor activity compared with senescence-accelerated mouse resistant 1 (SAMR1). There was no difference between SAMP6 and SAMR1 in the traction and wire hanging tests. In the rotating rod test, shorter retention times at each day in the accelerating version of the test were observed in SAMP6 compared with SAMR1, indicating a motor coordination deficit of SAMP6. To understand the mechanism involved, we focused on the dopamine system. Measurement of dopamine and its metabolites with HPLC revealed that the concentrations of dopamine in nucleus accumbens (NAcs) and cerebellum and of one or more dopamine metabolites in all tissues assayed were significantly higher in SAMP6 compared with SAMR1. Increases of dopamine transporter and dopamine receptor 1 (D1) in striatum, of dopamine receptor 3 (D3) in NAc, and of D1 and D3 in cerebellum in SAMP6 were observed. These results indicate that increased dopamine concentration in NAc and increased expression of D1 in striatum are possible cause(s) of the increased locomotor activity of SAMP6, and that increased D3 expression in cerebellum contributes to the motor coordination deficit of SAMP6.
通过一系列行为测试评估了快速老化小鼠易感6型（SAMP6）的运动功能：自发活动测试、牵引测试、悬线测试和转棒测试。与快速老化抗性小鼠1型（SAMR1）相比，SAMP6的自发活动增加。在牵引和悬线测试中，SAMP6和SAMR1之间没有差异。在转棒测试中，与SAMR1相比，SAMP6在加速版测试中每天的停留时间更短，表明SAMP6存在运动协调缺陷。为了解其中的机制，我们聚焦于多巴胺系统。用高效液相色谱法测量多巴胺及其代谢产物发现，与SAMR1相比，SAMP6伏隔核（NAc）和小脑中多巴胺的浓度以及所有检测组织中一种或多种多巴胺代谢产物的浓度显著更高。观察到SAMP6纹状体中多巴胺转运体和多巴胺受体1（D1）、NAc中多巴胺受体3（D3）以及小脑中D1和D3的增加。这些结果表明，NAc中多巴胺浓度增加和纹状体中D1表达增加可能是SAMP6自发活动增加的原因，并且小脑中D3表达增加导致了SAMP6的运动协调缺陷。
