Serotonergic influences on central respiratory activity: an in vitro study in the newborn rat.
The in vitro brainstem-spinal cord of the newborn rat has been used to study the central effects of serotonin (5-HT) on the brainstem respiratory motor control system. Brainstem superfusion with a medium containing 5-HT (30 microM) induced a short latency increase of respiratory frequency, often (60% of the experiments) followed by delayed tonic activity. Weaker concentrations of 5-HT (10-20 microM) were ineffective but prior application of drugs limiting 5-HT inactivation (pargyline and fluoxetine) revealed 5-HT effects. Changes in respiratory frequency are: (1) completely antagonized by methysergide; (2) not suppressed by 5-HT2 (ketanserine) and 5-HT3 (zacopride, GR3832F) antagonists; and (3) induced by 5-HT1 agonists (RU24969, buspirone). Since 5-HT2 agonists (DOI, alpha-methyl-5-HT) only evoked minor changes in frequency, the central action of 5-HT on the respiratory rhythm generator seems to depend on activation of 5-HT1 receptors. Tonic activity induced by 5-HT is: (1) antagonized by methysergide or ketanserine but not 5-HT3 antagonists; (2) induced by 5-HT2 but not 5-HT1 agonists; (3) still induced in the isolated spinal cord by 5-HT superfusion or 5-HT microinjection in the cervical ventral horn; and (4) sometimes replaced by rhythmic activity at a frequency different from that of respiration. Tonic activity does not involve the central circuitry responsible for respiration but depends on 5-HT2 receptors linked to spinal networks. These results suggest that 5-HT exerts a facilitory modulation on the respiratory rhythm generator through 5-HT1 medullary receptors and on motoneurons through 5-HT2 spinal receptors.
Morin
D
D
Département de Physiologie et Neurophysiologie, Faculté des Sciences et Techniques St. Jérôme, Marseille, France.
Hennequin
S
S
Monteau
R
R
Hilaire
G
G
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology; D003655:Decerebrate State; D008526:Medulla Oblongata / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D051381:Rats; D012119:Respiration / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D012702:Serotonin Antagonists; D012701:Serotonin