Serotonergic influences on central respiratory activity: an in vitro study in the newborn rat

Abstract

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 μM) 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 μM) 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-HT 2 (ketanserine) and 5-HT 3 (zacopride, GR38032F) anttagonists; and (3) induced by 5-HT 1 agonists (RU24969, buspirone). Since 5-HT 2 agonists (DOI, α-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-HT 1 receptors. Tonic activity induced by 5-HT is: (1) antagonized by methysergide or ketanserine but not 5-HT 3 antagonists; (2) induced by 5-HT 2 but not 5-HT 1 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-HT 2 receptors linked to spinal networks. These results suggest that 5-HT exerts facilittatory modulation on the respiratory rhythm generator through 5-HT 1 medullary receptors and on motoneurons through 5-HT 2 spinal receptors.