Partial depletion of dopamine in substantia nigra impairs motor performance without altering striatal dopamine neurotransmission
Partial depletion of dopamine in substantia nigra impairs motor performance without altering striatal dopamine neurotransmission
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DOI：
10.1111/j.1460-9568.2006.04953.x
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Bergquist, Filip
中科院分区：
文献类型：
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作者：
Andersson, Daniel R.;Nissbrandt, Hans;Bergquist, Filip
以往的数据表明，黑质中躯体树突状体多巴胺的释放影响运动的活动和协调性，但躯体树突状体多巴胺的释放与纹状体终末的多巴胺释放的相对重要性仍有待确定。我们用微透析法同时测定多巴胺神经递质，并用旋转棒试验评价运动能力，以探讨局部多巴胺耗竭对大鼠的影响。在黑质和纹状体局部应用囊泡型单胺转运体抑制剂四苯那津(100 MM)。黑质给药使黑质多巴胺透析液浓度降至基线的7%，全组织多巴胺含量降低60%。黑质多巴胺的耗竭与运动能力下降到治疗前的73+/-6%有关，但不改变同侧纹状体中透析液多巴胺的浓度。纹状体给药使纹状体多巴胺透析液浓度降低至基线的5%，并使躯体树突状细胞对运动活动的多巴胺反应增加一倍，但与运动能力或纹状体组织中多巴胺含量的变化无关。同时治疗黑质和纹状体可使运动能力下降至治疗前的58+/-5%。这项研究的结果表明，黑质多巴胺储存的部分耗尽会显著损害运动功能，而黑质多巴胺释放的增加可以抵消纹状体多巴胺传递的轻微损害。
Previous data indicate that the release of somatodendritic dopamine in substantia nigra influences motor activity and coordination, but the relative importance of somatodendritic dopamine release vs. terminal striatal dopamine release remains to be determined. We utilized simultaneous measurement of dopamine neurotransmission by microdialysis and motor performance assessment by rotarod test to investigate the effects of local dopamine depletion in rats. The vesicular monoamine transporter inhibitor tetrabenazine (100 mu m) was administered locally in substantia nigra as well as in striatum. Nigral tetrabenazine administration decreased nigral dopamine dialysate concentrations to 7% of baseline and whole-tissue dopamine content by 60%. Nigral dopamine depletion was associated with a reduction in motor performance to 73 +/- 6% of pretreatment value, but did not alter dialysate dopamine concentrations in the ipsilateral striatum. Striatal tetrabenazine administration decreased striatal dopamine dialysate concentrations to 5% of baseline and doubled the somatodendritic dopamine response to motor activity, but it was not associated with changes in motor performance or dopamine content in striatal tissue. Simultaneous treatment of substantia nigra and striatum reduced motor performance to 58 +/- 5% of the pretreatment value. The results of this study indicate that partial depletion of nigral dopamine stores can significantly impair motor functions, and that increased nigral dopamine release can counteract minor impairments of striatal dopamine transmission.