Functional role of striatal A2A, D2, and mGlu5 receptor interactions in regulating striatopallidal GABA neuronal transmission
Functional role of striatal A2A, D2, and mGlu5 receptor interactions in regulating striatopallidal GABA neuronal transmission
复制标题
DOI：
10.1111/jnc.13652
复制
发表时间：
2016-07-01
影响因子：
4.7
通讯作者：
Ferraro, Luca
中科院分区：
文献类型：
--
作者：
Beggiato, Sarah;Tomasini, Maria Cristina;Ferraro, Luca
本研究采用双探针微透析方法，在自由活动大鼠体内研究了腺苷（A2AR）、多巴胺（D2R）和代谢性谷氨酸受体（mGlu5R）的纹状体受体在调节大鼠基底神经节活性中的功能作用。特别是，D2R激动剂喹匹罗（10米，60分钟）的纹状体灌注降低了同侧白质GABA和谷氨酸水平，而CGS21680 （A2AR激动剂，1米，60分钟）的纹状体灌注对白质GABA和谷氨酸水平或喹匹罗诱导的效应均无效。mGlu5R激动剂(RS)-2-氯-5-羟基苯基甘氨酸（600M, 60min）在纹状体内灌注，其本身对白斑GABA和谷氨酸水平无效，部分抵消了喹匹罗的作用。当与CGS21680 （1M, 60min）联合使用时，(RS)-2-氯-5-羟基苯基甘氨酸（CHPG; 600M, 60min）完全抵消了喹匹罗（10M, 60min）诱导的同侧白质GABA和谷氨酸水平的降低。局部灌注mGlu5R拮抗剂MPEP （300M）或A2AR拮抗剂ZM 241385 （100 nM）可完全抵消这些作用。这些结果表明，A2ARs和mGlu5Rs在d2r介导的纹状体GABA神经元调控中协同作用。
In this study, the functional role of individual striatal receptors for adenosine (A2AR), dopamine (D2R), and the metabotropic glutamate receptor mGlu5R in regulating rat basal ganglia activity was characterized invivo using dual-probe microdialysis in freely moving rats. In particular, intrastriatal perfusion with the D2R agonist quinpirole (10M, 60min) decreased ipsilateral pallidal GABA and glutamate levels, whereas intrastriatal CGS21680 (A2AR agonist; 1M, 60min) was ineffective on either pallidal GABA and glutamate levels or the quinpirole-induced effects. Intrastriatal perfusion with the mGlu5R agonist (RS)-2-chloro-5-hydroxyphenylglycine (600M, 60min), by itself ineffective on pallidal GABA and glutamate levels, partially counteracted the effects of quinpirole. When combined with CGS21680 (1M, 60min), (RS)-2-chloro-5-hydroxyphenylglycine (CHPG; 600M, 60min) fully counteracted the quinpirole (10M, 60min)-induced reduction in ipsilateral pallidal GABA and glutamate levels. These effects were fully counteracted by local perfusion with the mGlu5R antagonist MPEP (300M) or the A2AR antagonist ZM 241385 (100 nM). These results suggest that A2ARs and mGlu5Rs interact synergistically in modulating the D2R-mediated control of striatopallidal GABA neurons.