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-HT(1A) receptor agonist had an age-dependent impact on the "CO(2) 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% CO(2) (all groups) and 12% O(2) (group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO(2) 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 CO(2) 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 CO(2) 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.

Sucking and swallowing rates after palatal anesthesia: an electromyographic study in infant pigs

“…Developmental differences in the role of oropharyngeal sensation during respiration have been noted in previous studies, and the same may be seen for the swallowing reflex as well (Litmanovitz et al 1994;Penatti et al 2006). Additionally, early studies of swallowing in decerebrate cats showed substantial variation in recordings from motor nerves following different oropharyngeal sensory stimulations that resulted in swallows in infants (Sumi 1967).…”

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

“…The advantage of 5,7-DHT is that it eliminates 5-HT neurons, and thus blocks release of both 5-HT and neuropeptides. The disadvantage is that 5,7-DHT typically reaches only a limited number of 5-HT neurons (Penatti et al, 2006). Therefore, data obtained using either of these approaches can be difficult to interpret.…”

Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome

“…5 A recent study involving chemical ablation of approximately 60% of medullary 5-HT neurons in neonatal piglets reported that males exhibited a blunted response to inspired carbon dioxide during sleep, whereas females responded normally. 40 Of note, this carbon dioxide response is modulated in part by 5-HT 1A receptors in the medullary raphé. 17 This experimental finding raises the possibility that in humans male infants may similarly be less sensitive to carbon dioxide than female infants, and that loss of medullary 5-HT 1A receptors, as observed in the SIDS cases in this study, may attenuate respiratory responses to hypercapnia to a greater extent in male compared with female infants, thus placing them at greater risk for SIDS.…”