HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 96/5/1909    most recent 00805.2003v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Messier, M. L. Articles by Nattie, E. E. Search for Related Content PubMed PubMed Citation Articles by Messier, M. L. Articles by Nattie, E. E.

Inhibition of medullary raphé serotonergic neurons has age-dependent effects on the CO₂ response in newborn piglets

Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756

Submitted 30 July 2003 ; accepted in final form 21 January 2004

Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO₂ in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome (48). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO₂ response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO₂ before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), a 5-HT_1A receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO₂ response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation (P < 0.001) between the percent change in the CO₂ response and piglet age. Younger piglets showed an exaggerated CO₂ response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO₂ response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age (P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less (P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO₂ response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO₂ sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.

brain stem; 8-hydroxy-2-di-n-propylaminotetralin; 5-HT_1A receptor; homeostatic physiology; sudden infant death syndrome

This article has been cited by other articles:

				M. Yamauchi, J. Dostal, H. Kimura, and K. P. Strohl Effects of buspirone on posthypoxic ventilatory behavior in the C57BL/6J and A/J mouse strains J Appl Physiol, August 1, 2008; 105(2): 518 - 526. [Abstract] [Full Text] [PDF]

				J. W. Brown, E. A. Sirlin, A. M. Benoit, J. M. Hoffman, and R. A. Darnall Activation of 5-HT1A receptors in medullary raphe disrupts sleep and decreases shivering during cooling in the conscious piglet Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R884 - R894. [Abstract] [Full Text] [PDF]

				L. Xia, T. Damon, M. M. Niblock, D. Bartlett Jr., and J. C. Leiter Unilateral microdialysis of gabazine in the dorsal medulla reverses thermal prolongation of the laryngeal chemoreflex in decerebrate piglets J Appl Physiol, November 1, 2007; 103(5): 1864 - 1872. [Abstract] [Full Text] [PDF]

				J. M. Hoffman, J. W. Brown, E. A. Sirlin, A. M. Benoit, W. H. Gill, M. B. Harris, and R. A. Darnall Activation of 5-HT1A receptors in the paragigantocellularis lateralis decreases shivering during cooling in the conscious piglet Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R518 - R527. [Abstract] [Full Text] [PDF]

				A. K. Curran and J. C. Leiter Respiratory: Baroreceptor-mediated inhibition of respiration after peripheral and central administration of a 5-HT1A receptor agonist in neonatal piglets Exp Physiol, July 1, 2007; 92(4): 757 - 767. [Abstract] [Full Text] [PDF]

				E. Nattie and A. Li Neurokinin-1 receptor-expressing neurons in the ventral medulla are essential for normal central and peripheral chemoreception in the conscious rat J Appl Physiol, December 1, 2006; 101(6): 1596 - 1606. [Abstract] [Full Text] [PDF]

				A. Li, S. Zhou, and E. Nattie Simultaneous inhibition of caudal medullary raphe and retrotrapezoid nucleus decreases breathing and the CO2 response in conscious rats J. Physiol., November 15, 2006; 577(1): 307 - 318. [Abstract] [Full Text] [PDF]

				D. S. Paterson, F. L. Trachtenberg, E. G. Thompson, R. A. Belliveau, A. H. Beggs, R. Darnall, A. E. Chadwick, H. F. Krous, and H. C. Kinney Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. JAMA, November 1, 2006; 296(17): 2124 - 2132. [Abstract] [Full Text] [PDF]

				E. M. Penatti, A. V. Berniker, B. Kereshi, C. Cafaro, M. L. Kelly, M. M. Niblock, H. G. Gao, H. C. Kinney, A. Li, and E. E. Nattie Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets J Appl Physiol, October 1, 2006; 101(4): 1177 - 1188. [Abstract] [Full Text] [PDF]

				S. Sood, E. Raddatz, X. Liu, H. Liu, and R. L. Horner Inhibition of serotonergic medullary raphe obscurus neurons suppresses genioglossus and diaphragm activities in anesthetized but not conscious rats J Appl Physiol, June 1, 2006; 100(6): 1807 - 1821. [Abstract] [Full Text] [PDF]

				R. A. Darnall, M. B. Harris, W. H. Gill, J. M. Hoffman, J. W. Brown, and M. M. Niblock Inhibition of Serotonergic Neurons in the Nucleus Paragigantocellularis Lateralis Fragments Sleep and Decreases Rapid Eye Movement Sleep in the Piglet: Implications for Sudden Infant Death Syndrome J. Neurosci., September 7, 2005; 25(36): 8322 - 8332. [Abstract] [Full Text] [PDF]

				N. C Taylor, A. Li, and E. E Nattie Medullary serotonergic neurones modulate the ventilatory response to hypercapnia, but not hypoxia in conscious rats J. Physiol., July 15, 2005; 566(2): 543 - 557. [Abstract] [Full Text] [PDF]

				N. C. Taylor, A. Li, A. Green, H. C. Kinney, and E. E. Nattie Chronic fluoxetine microdialysis into the medullary raphe nuclei of the rat, but not systemic administration, increases the ventilatory response to CO2 J Appl Physiol, November 1, 2004; 97(5): 1763 - 1773. [Abstract] [Full Text] [PDF]