Endogenous 5-HT2B receptor activation regulates neonatal respiratory activity in vitro

An implication of 5-HT2B receptors in central nervous system has not yet been clearly elucidated. We studied the role of different 5-HT2 receptor subtypes in the medullary breathing center, the pre-Bbtzinger complex, and on hypoglossal motoneurons in rhythmically active transversal slice preparations of neonatal rats and mice. Local microinjection of 5-HT2 receptor agonists revealed tonic excitation of hypoglossal motoneurons. Excitatory effects of the 5-HT2B receptor agonist BW723C86 could be blocked by bath application of LY272015, a highly selective 5-HTZB receptor antagonist. Excitatory effects of the 5-HT2A/B/c receptor agonist alpha-methyl 5-HT could be blocked by the preferential 5-HT2A receptor antagonist ketanserin. Therefore, 5-HT-induced excitation of by-poglossal motoneurons is mediated by convergent activation of 5-HT2A and 5-HT2B receptors. Local microinjection of BW723C86 in the pre-Botzinger complex increased respiratory frequency. Bath application of LY272015 blocked respiratory activity, whereas ketanserin had no effect. Therefore, endogenous 5-HT appears to support tonic action on respiratory rhythm generation via 5-HT2B receptors. In preparations of 5-HT2B receptor-deficient mice, respiratory activity appeared unaltered. Whereas BW723C86 and LY272015 had no effects, bath application of ketanserin disturbed and blocked rhythmic activity. This demonstrates a stimulatory role of endogenous 5-HT2B receptor activation at the pre-Bbtzinger complex and hypoglossal motoneurons that can be taken up by 5-HT2A receptors in the absence of 5-HT2B receptors. The presence of functional 5-HT2B receptors in the neonatal medullary breathing center indicates a potential convergent regulatory role of 5-HT2B and -(2A) receptors on the central respiratory network. (c) 2006 Wiley Periodicals, Inc.