Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets.
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.
Penatti
E M
EM
Department of Physiology, Dartmouth-Hitchcock Medical Center, Borwell Bldg., Lebanon, NH 03756-0001, USA. eliana.m.penatti@Dartmouth.edu
Berniker
A V
AV
Kereshi
B
B
Cafaro
C
C
Kelly
M L
ML
Niblock
M M
MM
Gao
H G
HG
Kinney
H C
HC
Li
A
A
Nattie
E E
EE
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D007231:Infant, Newborn; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012119:Respiration / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012737:Sex Factors; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D013398:Sudden Infant Death / Q000209:etiology* / Q000473:pathology; D013552:Swine
D002245:Carbon Dioxide; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin