{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:06:01Z","timestamp":1768014361837,"version":"3.49.0"},"reference-count":74,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:p>Medullary raph\u00e9 serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raph\u00e9 neurons decreases the ventilatory response to systemic CO<jats:sub>2<\/jats:sub>in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raph\u00e9, have been implicated in the sudden infant death syndrome ( 48 ). In this study, we ask whether serotonergic neurons in the medullary raph\u00e9 and extra-raph\u00e9 regions are involved in the CO<jats:sub>2<\/jats:sub>response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO<jats:sub>2<\/jats:sub>before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di- n-propylaminotetralin (8-OH-DPAT), a 5-HT<jats:sub>1A<\/jats:sub>receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO<jats:sub>2<\/jats:sub>response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation ( P &lt; 0.001) between the percent change in the CO<jats:sub>2<\/jats:sub>response and piglet age. Younger piglets showed an exaggerated CO<jats:sub>2<\/jats:sub>response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO<jats:sub>2<\/jats:sub>response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age ( P &lt; 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less ( P &lt; 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO<jats:sub>2<\/jats:sub>response in sleep. Inhibition of serotonergic medullary raph\u00e9 and extra-raph\u00e9 neurons decreases ventilatory CO<jats:sub>2<\/jats:sub>sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.<\/jats:p>","DOI":"10.1152\/japplphysiol.00805.2003","type":"journal-article","created":{"date-parts":[[2004,4,9]],"date-time":"2004-04-09T00:57:57Z","timestamp":1081472277000},"page":"1909-1919","source":"Crossref","is-referenced-by-count":78,"title":["Inhibition of medullary raph\u00e9 serotonergic neurons has age-dependent effects on the CO<sub>2<\/sub>response in newborn piglets"],"prefix":"10.1152","volume":"96","author":[{"given":"Michelle L.","family":"Messier","sequence":"first","affiliation":[{"name":"Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene E.","family":"Nattie","sequence":"additional","affiliation":[{"name":"Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(89)90154-8"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(70)90056-3"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.80.1.108"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(98)00050-4"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01426-2"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00758-0"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)64132-1"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1038\/nn848"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4179(85)90141-6"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-03-00977.2002"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90007-4"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.3.971"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1964.tb03945.x"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/24.5.514"},{"key":"REF15","unstructured":"Darnall RA, Harris M, Filiano JJ, and Gill W.Dialysis of 8-OH-DPAT into the juxta-facial paragigantocellularis lateralis (PGCL) disrupts sleep architecture in piglets. 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