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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of newborn piglets.
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Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of newborn piglets.

机译:兴奋性氨基酸受体拮抗剂可减少缺氧引起的新生仔猪纹状体细胞外多巴胺增加。

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The present study tested the hypothesis that the increase in extracellular striatal dopamine during hypoxia is least partly associated with activation of N-methyl-D-aspartate (NMDA) and/or non-NMDA excitatory amino acid receptors. Studies were performed in anesthetized and mechanically ventilated 2-3 days old piglets. Hypoxic insult was induced by decreasing the oxygen fraction in inspired gas (FiO2) from 22 to 7% for 1 h, followed by 1 h reoxygenation at 22%. Cortical oxygen pressure was measured optically by oxygen dependent quenching of phosphorescence, and extracellular striatal dopamine was measured using in vivo microdialysis. The microdialysis probes were perfused with Ringer solution +/- 50 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) or 50 microM 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). One hour of hypoxia decreased the cortical oxygen pressure from 46 +/- 3 Torr to 10 +/- 1.8 Torr. In striatum perfused with Ringer, statistically significant increase in extracellular dopamine, to 1050 +/- 310% of control, was observed after 20 min of hypoxia. By 40 min of hypoxia the extracellular level of dopamine increased to 4730 +/- 900% of control; by the end of the hypoxic period the values increased to 18,451 +/- 1670% of control. The presence of MK-801 in the perfusate significantly decreased the levels of extracellular dopamine during hypoxia. At 20, 40 and 60 min of hypoxia extracellular level of dopamine increased to 278 +/- 94% of control, 1530 +/- 339% of control and 14,709 +/- 1095 of control, respectively. The presence of NBQX caused a statistically significant decrease, by about 30%, in the extracellular dopamine compared to control, only at the end of the hypoxic period. It can be concluded that in striatum of newborn piglets, the excitatory NMDA receptors but not the non-NMDA receptors may be modulating the changes in extracellular levels of dopamine. The NMDA receptor antagonist, MK-801, may exert part of its reported neuroprotective effect to hypoxic stress in striatum by decreasing the levels of extracellular dopamine.
机译:本研究检验了以下假设:缺氧期间细胞外纹状体多巴胺的增加至少部分与N-甲基-D-天冬氨酸(NMDA)和/或非NMDA兴奋性氨基酸受体的激活有关。在麻醉和机械通风的2-3天大的仔猪中进行研究。通过将吸入气体(FiO2)中的氧气分数从22降低到7%持续1 h,然后再以22%的比例再充氧1 h,来引起缺氧性侮辱。通过氧依赖性的磷光猝灭来光学测量皮层氧气压力,并使用体内微透析测量细胞外纹状体多巴胺。微透析探针用林格溶液+/- 50 microM(+)-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚-5,10-亚胺马来酸酯(MK-801)或50 microM 2,3-二羟基-6-硝基-7-氨磺酰基-苯并(F)喹喔啉(NBQX)。一小时的缺氧将皮层氧气压力从46 +/- 3托降低到10 +/- 1.8托。在缺氧20分钟后,观察到用林格灌注的纹状体中,细胞外多巴胺在统计学上显着增加,达到对照的1050 +/- 310%。缺氧40分钟后,多巴胺的细胞外水平增加至对照的4730 +/- 900%;到缺氧期结束时,该值增加到对照的18,451 +/- 1670%。灌注液中MK-801的存在显着降低了缺氧期间细胞外多巴胺的水平。在缺氧的20、40和60分钟,多巴胺的细胞外水平分别增加到对照的278 +/- 94%,对照的1530 +/- 339%和对照的14709 +/- 1095。仅在缺氧期结束时,与对照组相比,NBQX的存在引起细胞外多巴胺的统计学显着降低,降低幅度约为30%。可以得出结论,在新生仔猪的纹状体中,兴奋性NMDA受体而不是非NMDA受体可能正在调节多巴胺细胞外水平的变化。 NMDA受体拮抗剂MK-801可通过降低细胞外多巴胺的水平来发挥其对纹状体缺氧应激的部分神经保护作用。

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