Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets

Abstract

Acute inhibition of serotonergic (5-HT) neurons in the medullary raphé (MR) using a 5-HT1A receptor agonist had an age-dependent impact on the “CO2 response” of piglets ( 33 ). Our present study explored the effect of chronic 5-HT neuron lesions in the MR and extra-raphé on the ventilatory response to hypercapnia and hypoxia in piglets, with possible implications on the role of 5-HT in the sudden infant death syndrome. We established four experimental groups. Group 1 ( n = 11) did not undergo any treatment. Groups 2, 3, and 4 were injected with either vehicle or the neurotoxin 5,7-dihydroxytryptamine in the cisterna magna during the first week of life ( group 2, n = 9; group 4, n = 11) or second week of life ( group 3, n = 10). Ventilation was recorded in response to 5% CO2 (all groups) and 12% O2 ( group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO2 sensitivity during early postnatal development. Overall, considerable lesions of 5-HT neurons (up to 65% decrease) in the MR and extra-raphé had no impact on the CO2 response, regardless of injection time. Postlesion raphé plasticity could explain why we observed no effect. 5,7-Dihydroxytryptamine-treated males, however, did present a lower CO2 response during sleep. Hypoxia significantly altered the frequency during sleep in lesioned piglets. Further studies are necessary to elucidate the role of plasticity, sex, and 5-HT abnormalities in sudden infant death syndrome.