Serotonergic and noradrenergic effects on respiratory neural discharge in the medullary slice preparation of neonatal rats.
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-Botzinger 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 "mu"M; P < 0.05); (2) via pressure injection into the region of the pre-Botzinger 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)- "alpha"-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (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 "mu"M). NA caused a reduction of respiratory burst frequency when applied to the bathing medium (40 +/- 15%; 100 "mu"M; P < 0.05) or when pressure injected into the region of the pre-Botzinger complex (22 +/- 11%; < 25 pmol; P < 0.05). These effects were blocked by the bath application of the "alpha"2-receptor antagonist idazoxan (2 "mu"M). 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.HCl, 5 "mu"M) and blocked by the 5-HT2 receptor antagonist ketanserine tartrate (30-40 "mu"M). The NA-induced XII nerve tonic discharge was mimicked by the "alpha"1-receptor agonist phenylephrine HCl (500 nM) and blocked by the "alpha"1-receptor antagonist prozasin HCl (1 "mu"M).
Al-Zubaidy
Z A
ZA
Division of Neuroscience, Department of Physiology, 513 HMRC, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Erickson
R L
RL
Greer
J J
JJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology*; D008784:Methysergide / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012890:Sleep / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D012702:Serotonin Antagonists; D012701:Serotonin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D009638:Norepinephrine; D008784:Methysergide