Serotonin receptor subtypes involved in vagus nerve stimulation-induced phrenic long-term facilitation in rats

Episodic vagus nerve stimulation (VNS) induces phrenic long-term facilitation (LTF, a persistent augmentation of phrenic nerve activity after the stimulation ends), sensitive to the serotonin 5-HT1,2.5,6,7 receptor antagonist methysergide and similar to that elicited by episodic hypoxia or carotid sinus nerve stimulation. This study examined the effect of ketanserin (5-HT2 antagonist) or clozapine (5-HT2,6,7 antagonist) on VNS-induced LTF in anesthetized, vagotomized, paralyzed and ventilated rats to determine which receptor subtype(s) is involved. Three episodes of 5 min VNS (50 Hz, 0.1 ms, similar to 500 muA) with 5 min intervals elicited phrenic LTF in control (amplitude: 38% above baseline at 60 min post-VNS) and ketanserin (2 mg(.)kg(-1), i.p.) pre-treated rats (45%), but not clozapine (3 mg(.)kg(-1)) rats (8%). These data suggest that unlike hypoxia-induced LTF (5-HT2 receptor-dependent), VNS-induced LTF requires non-5-HT2 serotonin receptors, perhaps 5-HT6 and/or 5-HT7 subtype(s). (C) 2004 Elsevier Ireland Ltd. All rights reserved.