Role of 5-HT₁(A) receptors in induction and preservation of phrenic long-term facilitation in rats

Abstract

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.