5-ht2 receptor subtypes mediate different long-term changes in GABAergic activity to parasympathetic cardiac vagal neurons in the nucleus ambiguus

Serotonin (5-HT), and in particular 5-HT2 receptors, play an important role in cardiorespiratory function within the brainstem. In addition, abnormalities in the 5-HT system have been implicated in many cardiorespiratory disorders, including sudden infant death syndrome. However, little is known about the mechanisms of action of 5-HT2 receptors in altering the activity of parasympathetic cardiac neurons in the brainstem. In this study we examined the effects of activation of different subtypes of 5-HT2 receptors on spontaneous and respiratory-evoked GABAergic neuro- transmission to cardioinhibitory vagal neurons within the nucleus ambiguus as well as rhythmic fictive inspiratory-related activity in rats. A single application of alpha-Me-5-hydroxytryptamine maleate (alpha-Me-5-HT), a 5-HT2 receptor agonist, did not significantly alter the frequency of spontaneous or respiratory-evoked GABAergic inhibitory postsynaptic currents (IPSCs) in cardiac vagal neurons. However, repetitive successive applications of a-Me-5-HT elicited a long-lasting ( l h) decrease in the frequency of spontaneous as well as inspiratory-related GABAergic IPSCs to cardiac vagal neurons. This study demonstrates multiple, but not single applications of the 5-HT2 receptor agonist a-Me-5-HT caused a long-lasting inhibition of both spontaneous and fictive inspiratory-related GABAergic neurotransmission to CVNs, which can be prevented by the 5-HT2B receptor antagonist SB204741, but persisted with the 5-HT2A/2C receptor antagonist ketanserin. The 5-HT2 receptor agonist a-Me-5-HT also reversibly and transiently excited central fictive inspiratory activity, which was abolished by ketanserin, but was unaffected by the 5-HT2B receptor antagonist SB204741. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.