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J Appl Physiol 101: 1177-1188, 2006. First published June 8, 2006; doi:10.1152/japplphysiol.00376.2006
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Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets

E. M. Penatti,1 A. V. Berniker,1 B. Kereshi,1 C. Cafaro,1 M. L. Kelly,2 M. M. Niblock,1 H. G. Gao,1 H. C. Kinney,3 A. Li,1 and E. E. Nattie1

1Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire; 2Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut; and 3Department of Pathology, Children's Hospital Boston, Boston, Massachusetts

Submitted 29 March 2006 ; accepted in final form 26 May 2006

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.

5,7-dihydroxytryptamine; sudden infant death syndrome; raphé; plasticity; serotonin


Address for reprint requests and other correspondence: E. M. Penatti, Dept. of Physiology, Dartmouth-Hitchcock Medical Center, Borwell Bldg., Lebanon, NH 03756–0001 (e-mail: eliana.m.penatti{at}Dartmouth.edu)




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