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

1 Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire; 2 Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut; and 3 Department 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-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. 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 )