Early Onset of Ventilatory and Airway Response to Hypercapnia is Mediated by Medullary 5-HT_1A Receptors in Infant Rats

Abstract

: Medullary 5-hydroxytryptamine 5-HT neurons are involved in ventilatory responses to hypercapnia. Underdeveloped medullary 5-HT neurons and reduced 5-HT 1A receptor binding activity in the dorsomedial medulla oblongata DMM have been found in infants with sudden infant death syndrome SIDS . The DMM includes the solitary tract nucleus, which receives primary afferent inputs from the lung, and the hypoglossal nucleus, which affects genioglossal muscle tone. We hypothesized that hypercapnia would elicit 5-HT release in the DMM and that local 5-HT 1A receptors would affect ventilatory and airway responses to hypercapnia. This hypothesis was investigated in unanesthetized infant Wistar rats by microdialysis of the DMM coupled with double-chamber plethysmography. After microdialysis probe placement, the rats were acclimatized to the chamber for over 5 h, and arti cial cerebrospinal uid aCSF or a 5-HT 1A receptor antagonist, WAY-100635, was then perfused into the DMM, and extracellular fluid was collected. Respiratory ow curves were recorded while the rats inhaled ve concentrations of CO 2 in O 2 for 10 min each 0 100 O 2 , 5 , 7 , 9 , and 0 again . 5-HT concentration was measured using high-performance liquid chromatography with electrochemical detection. 5-HT release in the DMM and hypercapnic ventilatory and airway responses increased dose dependently with CO 2 concentration during both aCSF and WAY-100635 perfusion, with no difference between groups. However, early-onset ventilatory and airway responses to hypercapnia were signicantly delayed or reduced by WAY-100635 perfusion in the DMM. These results suggest that 5-HT release in the DMM is dependent on hypercapnia, while early ventilatory and airway responses to hypercapnia are mediated by 5-HT 1A receptors in the DMM. Blunted early onset of hypercapnic ventilatory and airway responses may be one cause of SIDS.