Department of Neuroscience, University of Split School of Medicine, Split, Croatia.
Respir Physiol Neurobiol. 2011 Jan 31;175(1):146-52. doi: 10.1016/j.resp.2010.10.005. Epub 2010 Oct 28.
The aim was to investigate the role of 5-HT₁(A) receptor activation in induction and preservation of phrenic long-term facilitation (pLTF) at two different time points, before exposures to episodic hypoxia and after pLTF was induced. Adult, male, urethane anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypoxia (AIH) protocol. Experimental groups of animals received an intravenous injection of WAY-100635, before the onset of the first hypoxic stimulus (WAY0), and after pLTF was induced (WAY60). Peak phrenic nerve activity (pPNA), burst frequency (f), and respiratory rhythm parameters were analyzed during the five hypoxic exposures (TH1-5), as well as at 15 min (T15), 30 min (T30), and 60 min (T60) after the end of the last hypoxic episode. In the control group, pPNA was elevated from baseline (121.6 ± 7.3%, P < 0.001) at 60 min after episodic hypoxia indicating pLTF. Administration of WAY-100635 prior to hypoxic stimulation prevented the induction of pLTF. Additionally, administration of WAY-100635 after pLTF developed impaired preservation of pLTF. In conclusion, there is an important role for 5-HT₁(A) receptors in induction as well as in preservation of pLTF in urethane anesthetized rats.
目的是在两个不同时间点，即在暴露于间歇性缺氧之前和诱导长时程膈神经易化（pLTF）之后，研究 5-HT₁(A)受体激活在诱导和维持 pLTF 中的作用。成年雄性乌拉坦麻醉、迷走神经切断、麻痹和机械通气的 Sprague-Dawley 大鼠接受急性间歇性缺氧（AIH）方案。实验组动物在第一次缺氧刺激前（WAY0）和 pLTF 诱导后（WAY60）静脉注射 WAY-100635。在五次缺氧暴露（TH1-5）期间以及缺氧结束后 15 分钟（T15）、30 分钟（T30）和 60 分钟（T60）分析峰值膈神经活动（pPNA）、爆发频率（f）和呼吸节律参数。在对照组中，pPNA 在缺氧刺激后 60 分钟从基线升高（121.6±7.3%，P<0.001），表明出现 pLTF。在缺氧刺激前给予 WAY-100635 可防止 pLTF 的诱导。此外，在 pLTF 发展后给予 WAY-100635 会损害 pLTF 的维持。总之，5-HT₁(A)受体在乌拉坦麻醉大鼠的 pLTF 诱导和维持中起重要作用。
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