{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:46:38Z","timestamp":1771026398177,"version":"3.50.1"},"reference-count":45,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost (Croatian Science Foundation)","doi-asserted-by":"publisher","award":["09\/165"],"award-info":[{"award-number":["09\/165"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost (Croatian Science Foundation)","doi-asserted-by":"publisher","award":["5935"],"award-info":[{"award-number":["5935"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:p>Intermittent hypercapnia evokes prolonged depression of phrenic nerve activity (phrenic long-term depression, pLTD). This study was undertaken to investigate the role of 5-HT and \u03b12-adrenergic receptors in the initiation of pLTD. Adult male urethane-anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to a protocol of acute intermittent hypercapnia (AIHc; 5 episodes of 15% CO<jats:sub>2<\/jats:sub>in air, each episode lasting 3 min). The experimental group received microinjection of the selective 5-HT<jats:sub>1A<\/jats:sub>receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), the broad-spectrum 5-HT antagonist methysergide, or the \u03b12-adrenergic antagonist yohimbine, whereas the control group received microinjection of 0.9% saline into the caudal raphe region. Peak phrenic nerve activity (pPNA) and burst frequency ( f) were analyzed during baseline (T0), during 5 hypercapnic episodes (THc1\u2013THc5), and at 15, 30, and 60 min after the end of the last hypercapnic episode. In the control group, pPNA decreased 60 min after the end of the last hypercapnic episode compared with baseline values, i.e., pLTD developed ( P = 0.023). In the 8-OH-DPAT group, pPNA significantly decreased at T15, T30, and T60 compared with baseline values, i.e., pLTD developed ( P = 0.01). In the methysergide and yohimbine groups, AIHc did not evoke significant changes of the pPNA at T15, T30, and T60 compared with baseline values. In conclusion, activation of 5-HT<jats:sub>1A<\/jats:sub>receptors accentuated induction of pLTD, whereas blockade of \u03b12-adrenergic receptors prevented development of pLTD following AIHc in anesthetized rats. These results suggest that chemical modulation of 5-HT and \u03b12-adrenergic receptors in raphe nuclei affects hypercapnia-induced pLTD, offering important insights in understanding the mechanisms involved in development of respiratory plasticity.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Hypercapnia is a concomitant feature of many breathing disorders, including obstructive sleep apnea. In this study, acute intermittent hypercapnia evoked development of phrenic long-term depression (pLTD) 60 min after the last hypercapnic episode that was preserved if the selective 5-HT<jats:sub>1A<\/jats:sub>receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide was microinjected in the caudal raphe region before the hypercapnic stimulus. This study highlights that both 5-HT and adrenergic receptor activation is needed for induction of pLTD in urethane-anesthetized rats following intermittent hypercapnia exposure.<\/jats:p>","DOI":"10.1152\/jn.00776.2017","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T20:31:29Z","timestamp":1522873889000},"page":"321-329","source":"Crossref","is-referenced-by-count":11,"title":["Phrenic long-term depression evoked by intermittent hypercapnia is modulated by serotonergic and adrenergic receptors in raphe nuclei"],"prefix":"10.1152","volume":"120","author":[{"given":"Ivona","family":"Stipica Safic","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Split School of Medicine, Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Pecotic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Split School of Medicine, Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Pavlinac Dodig","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Split School of Medicine, Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoran","family":"Dogas","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Split School of Medicine, Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoran","family":"Valic","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Split School of Medicine, Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Valic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Split School of Medicine, Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(77)90040-5"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)01239-5"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-03-00760.1991"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.84.6.2099"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(01)00280-8"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-14-06239.2002"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2008.03.005"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(81)90646-6"},{"key":"B9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0022-3565(25)21386-6","volume":"250","author":"Bobker DH","year":"1989","journal-title":"J Pharmacol Exp Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903470106"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(81)91040-4"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/BF01250667"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018269"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018846"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00524.2010"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1993.264.6.R1035"},{"key":"B17","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/S0022-3565(25)12944-3","volume":"277","author":"Haddjeri N","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700968"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00896.2005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(96)00076-8"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.84.4.1198"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(95)00030-H"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-0618(97)00019-7"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902420105"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S1095-6433(01)00393-2"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.178053"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(69)90185-1"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00481-J"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2008.045153"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.04.010"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00523.2002"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2008.01853.x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1113\/EP085634"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2010.10.005"},{"key":"B35","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos GW","year":"2005"},{"key":"B36","first-page":"167","volume":"60","author":"Pecotic R","year":"2009","journal-title":"J Physiol Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(90)90284-7"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/BF01248998"},{"key":"B39","doi-asserted-by":"crossref","first-page":"133","DOI":"10.33549\/physiolres.933012","volume":"65","author":"Stipica I","year":"2016","journal-title":"Physiol Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.083873"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-010-2161-2"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1113\/EP085161"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903400103"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01273.2007"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00702.2011"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00776.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T12:45:18Z","timestamp":1751546718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00776.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,1]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,7,1]]}},"alternative-id":["10.1152\/jn.00776.2017"],"URL":"https:\/\/doi.org\/10.1152\/jn.00776.2017","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,1]]}}}