Effects of sarizotan on the corticostriatal glutamate pathways
Effects of sarizotan on the corticostriatal glutamate pathways
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DOI：
10.1002/syn.20195
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发表时间：
2005-12-01
期刊：
影响因子：
2.3
通讯作者：
Ferraro, L
中科院分区：
文献类型：
--
作者：
Antonelli, T;Fuxe, K;Ferraro, L
沙立唑坦是一种对D-3和D-4受体具有额外亲和力的5-HT1A激动剂，研究了沙立唑坦对清醒大鼠皮质纹状体谷氨酸通路的影响。沙立唑坦系统给药（0.1 ~ 10 mg/kg s.c）或灌注到运动皮质（10 μ M）可使皮质和纹状体谷氨酸水平降低20 ~ 30%。系统性沙唑坦对皮质和纹状体谷氨酸水平的抑制作用可通过5-HT1A拮抗剂WAY100135 （10 μ M）皮质内灌注抵消。这些发现表明，沙唑坦的抗运动障碍特性可能是通过其在运动皮层中的5-HT1A激动剂作用介导的，导致皮质纹状体谷氨酸通路活性降低，纹状体GABA通路活性降低，介导运动抑制。
The effects of sarizotan, a 5-HT1A agonist with additional affinity for D-3 and D-4 receptors, have been studied on the corticostriatal glutamate pathways using dual-probe microdialysis in the awake rat. Sarizotan given systemically (0.1-10 mg/kg s.c.) or perfused into the motor cortex (10 mu M) produced 20-30% reduction of cortical and striatal glutamate levels. The inhibitory effects of the systemic sarizotan on cortical and striatal glutamate levels were counteracted by intracortical perfusion with the 5-HT1A antagonist WAY100135 (10 mu M). These findings suggest that the anti-dyskinetic properties of sarizotan could be mediated via its 5-HT1A agonist actions in the motor cortex, leading to reduced activity in the corticostriatal glutamate pathways with reduced activation of the striatopallidal GABA pathway mediating motor inhibition.