Understanding of regulatory mechanism of motor activity using D1 and D2 dopamine receptor gene-modified mice

在帕金森病中，黑质纹状体多巴胺神经元的退化导致多巴胺的耗竭和运动障碍。已知纹状体中棘神经元表达的D_1和D_2多巴胺受体(D_1R、D_2R)参与运动控制。然而，D1R和D2R对运动控制的调控机制尚不清楚。在本研究中，我们发现由Tet-Off系统控制的条件性表达D1R的小鼠在成年期抑制D1R表达时，在家庭中的运动活动减少。这一发现与D1R KO小鼠运动活动的显著增加相反。提示D1R在小鼠发育过程中表达的存在或缺失与成体阶段运动活动的上调或下调密切相关。

In Parkinson disease the degeneration of nigro-striatal dopamine neuron leads to depletion of dopamine and motor deficit. It is known that D1 and D2 dopamine receptors (D1R, D2R) expressed in the medium spiny neurons of striatum are involved to motor control. However, the regulatory mechanism of motor control via D1R and D2R remains to be clarified. In this study we found the conditional D1R-expressing mice controlled by Tet-off system showed decrease of motor activity in the homecage when D1R expression was suppressed in adult stage. This finding was opposite to the marked increase of motor activity of D1R KO mice. These suggest the presence or absence of D1R expression during mouse development is closely related to up-regulation or down-regulation of motor activity in adult stage.