Intravenously administered hypocretin-1 alters brain amino acid release:: an in vivo microdialysis study in rats
Intravenously administered hypocretin-1 alters brain amino acid release:: an in vivo microdialysis study in rats
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DOI：
10.1113/jphysiol.2002.038729
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发表时间：
2003-04-15
影响因子：
5.5
通讯作者：
Siegel, JM
中科院分区：
文献类型：
--
作者：
John, J;Wu, MF;Siegel, JM
我们已经报道了静脉注射下丘脑泌素（Hcrt或食欲素）逆转遗传性发作性睡病犬的发作性睡病症状。我们还报道了犬遗传性发作性睡病的发病伴随着前脑区域的退行性变化，特别是隔核和杏仁核。在目前的体内微透析研究中，我们已经调查了静脉注射给药的Hcrt-1（食欲素-A）麻醉大鼠的谷氨酸和GABA的释放在杏仁核，一个区域与中度Hcrt神经支配，并在小脑皮质，一个区域与稀疏或没有Hcrt神经支配。我们发现，静脉注射Hcrt引起杏仁核内谷氨酸释放的显著（> 60%）和持续（> 50分钟）增加，但小脑皮质的释放没有变化。我们没有检测到GABA释放的显着变化。当使用无钙人工脑脊液作为微透析灌流液时，Hcrt-1不再产生谷氨酸释放的增加。在中枢神经系统的某些核团中，Hcrt可能通过钙依赖性调节谷氨酸的释放而发挥作用。
We have reported that intravenous administration of hypocretin (Hcrt or orexin) reverses the symptoms of narcolepsy in genetically narcoleptic dogs. We have also reported that the onset of symptoms in canine genetic narcolepsy is accompanied by degenerative changes in forebrain regions, particularly the septal nucleus and amygdala. In the present in vivo microdialysis study we have investigated the effect of intravenous administration of Hcrt-1 (orexin-A) to anaesthetized rats on glutamate and GABA release in the amygdala, a region with moderate Hcrt innervation, and in the cerebellar cortex, a region with sparse or no Hcrt innervation. We found that intravenous Hcrt administration caused a marked (> 60%) and sustained (> 50 min) increase in glutamate release within the amygdala, but no change in release in the cerebellar cortex. We did not detect a significant change in GABA release. When calcium-free artificial cerebrospinal fluid was used as the microdialysis perfusate, Hcrt-1 no longer produced an increase in glutamate release. Hcrt may act via the calcium-dependent regulation of glutamate release in certain nuclei of the central nervous system.