Serotonergic and noradrenergic effects on respiratory neural discharge in the medullary slice preparation of neonatal rats

Publisher Website
Google Scholar
Abstract
Rhythmically active medullary slice preparations isolated from neonatal rats (postnatal days 0-3, P0-P3) were used to study the modulation of respiraory rhythmogenesis and hypoglossal (XII) nerve discharge by serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NA). 5-HT, NA and their respective receptor agonists and antagonists were applied either to the bathing medium or focally via pressure injection into regions encompassing the pre-Bötzinger complex or XII motoneurons. The effects of endogenously released 5-HT were also studied by chemical stimulation of neurons within the raphe obscurus. The frequency of respiratory burst discharge was increased when 5-HT was applied: (1) to the bathing medium (37±16%; 30 µM; P < 0.05); (2) via pressure injection into the region of the pre-Bötzinger complex (22 ± 14%; < 25 pmol; P < 0.05); or (3) endogenously released in response to activation of neurons within the raphe obscurus via pressure injection of (R,S)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydro-bromide (AMPA, 34 ± 15%; P < 0.05) or 5-HT (33 ± 5%; P < 0.05). All of these effects were antagonized by bath application of methysergide (30-40 µM). NA caused a reduction of respiratory burst frequency when applied to the bathing medium (40 ± 15%; 100 µM; P < 0.05) or when pressure injected into the region of the pre-Bötzinger complex (22 ± 11 %; < 25 pmol; P < 0.05). These effects were blocked by the bath application of the a2-receptor antagonist idazoxan (2 µM). 5-HT and NA both caused an augmentation of tonic discharge of XII nerves when applied either to the bathing medium or via pressure injection into the XII motoneuron pool. The 5-HT-induced XII nerve tonic discharge was mimicked by the 5-HT2 receptor agonist R(-)2-(2,5-dimethoxy-4-iodophenyl) (DOI.HC1, 5 µM) and blocked by the 5-HT2 receptor antagonist ketanser-ine tartrate (30-40 µM). The NA-induced XII nerve tonic discharge was mimicked by the α1-receptor agonist phenylephrine HC1 (500 µM) and blocked by the α1-receptor antagonist prozasin HC1 (@#@ 1 µM).