{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:27:35Z","timestamp":1784179655776,"version":"3.55.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:p>The medullary 5-HT system has potent effects on heart rate and breathing in adults. We asked whether this system mitigates the respiratory instability and bradycardias frequently occurring during the neonatal period. 5,7-Dihydroxytryptamine (5,7-DHT) or vehicle was administered to rat pups at postnatal day 2 (P2), and we then compared the magnitude of bradycardias occurring with disruptions to eupnea in treated and vehicle control littermates at P5\u20136 and P10\u201312. We then used a novel method that would allow accurate assessment of the ventilatory and heart rate responses to near square-wave challenges of hypoxia (10% O<jats:sub>2<\/jats:sub>), hypercapnia (5 and 8% CO<jats:sub>2<\/jats:sub>in normoxia and hyperoxia), and asphyxia (8% CO<jats:sub>2<\/jats:sub>-10% O<jats:sub>2<\/jats:sub>), and to the induction of the Hering-Breuer inflation reflex (HBR), a potent, apnea-inducing reflex in newborns. The number of 5-HT-positive neurons was reduced \u223c80% by drug treatment. At both ages, lesioned animals had considerably larger bradycardias during brief apnea; at P5\u20136, average and severe events were \u223c50% and 70% greater, respectively, in lesioned animals ( P = 0.002), whereas at P10\u201312, events were \u223c 23% and 50% greater ( P = 0.018). However, lesioning had no effect on the HR responses to sudden gas challenge or the HBR. At P5\u20136, lesioned animals had reduced breathing frequency and ventilation (V\u0307e), but normal V\u0307e relative to metabolic rate (V\u0307e\/V\u0307o<jats:sub>2<\/jats:sub>). At P10\u201312, lesioned animals had a more unstable breathing pattern ( P = 0.04) and an enhanced V\u0307e response to moderate hypercapnia ( P = 0.007). Within the first two postnatal weeks, the medullary 5-HT system plays an important role in cardiorespiratory control, mitigating spontaneous bradycardia, stabilizing the breathing pattern, and dampening the hypercapnic V\u0307e response.<\/jats:p>","DOI":"10.1152\/ajpregu.00122.2009","type":"journal-article","created":{"date-parts":[[2009,4,16]],"date-time":"2009-04-16T01:45:16Z","timestamp":1239846316000},"page":"R1783-R1796","source":"Crossref","is-referenced-by-count":44,"title":["Severe spontaneous bradycardia associated with respiratory disruptions in rat pups with fewer brain stem 5-HT neurons"],"prefix":"10.1152","volume":"296","author":[{"given":"Kevin J.","family":"Cummings","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn G.","family":"Commons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth C.","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene E.","family":"Nattie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20832"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050089"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1978.sp012152"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157871"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.94.07040786"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1997.272.4.R1135"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(96)00140-3"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.01.088"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.072371"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.08.015"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.02.016"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.160.2.203"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2007.06.002"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1159\/000244052"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(99)00103-6"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00992.2003"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00584.2004"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2008.08.003"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4729-07.2008"},{"key":"R20","unstructured":"Hoppenbrouwers T, Hodgman JE, Harper RM, Hofmann E, Sterman MB, McGinty DJ.Polygraphic studies of normal infants during the first six months of life: III. 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