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: 97/5/1763    most recent 00496.2004v1 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 (8) Citing Articles via Google Scholar Google Scholar Articles by Taylor, N. C. Articles by Nattie, E. E. Search for Related Content PubMed PubMed Citation Articles by Taylor, N. C. Articles by Nattie, E. E.

Chronic fluoxetine microdialysis into the medullary raphe nuclei of the rat, but not systemic administration, increases the ventilatory response to CO₂

¹Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756; and Departments of ²Pathology and ³Neurology Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Submitted 7 May 2004 ; accepted in final form 16 July 2004

In conscious rats, focal CO₂ stimulation of the medullary raphe increases ventilation, whereas interference with serotonergic function here decreases the ventilatory response to systemic hypercapnia. We sought to determine whether repeated administration of a selective serotonin reuptake inhibitor in this region would increase the ventilatory response to hypercapnia in unanesthetized rats. In rats instrumented with electroencephalogram-electromyogram electrodes, 250 or 500 µM fluoxetine or artificial cerebrospinal fluid (aCSF) was microdialyzed into the medullary raphe for 30 min daily over 15 days. To compare focal and systemic treatment, two additional groups of rats received 10 mg·kg^–1·day^–1 fluoxetine or vehicle systemically. Ventilation was measured in normocapnia and in 7% CO₂ before treatment (day 0), acutely (days 1 or 3), on day 7, and on day 15. There was no change in normocapnic ventilation in any treatment group. Rats that received 250 µM fluoxetine microdialysis showed a significant 13% increase in ventilation in wakefulness during hypercapnia on day 7, due to an increase in tidal volume. In rats microdialyzed with 500 µM fluoxetine, there were 16 and 32% increases in minute ventilation during hypercapnia in wakefulness and sleep on day 7, and 20 and 28% increases on day 15, respectively, again due to increased tidal volume. There was no change in the ventilatory response to CO₂ in rats microdialyzed with aCSF or in systemically treated rats. Chronic fluoxetine treatment in the medullary raphe increases the ventilatory response to hypercapnia in an unanesthetized rat model, an effect that may be due to facilitation of chemosensitive serotonergic neurons.

brain stem; chemoreceptor; serotonin transporter; selective serotonin reuptake inhibitor

This article has been cited by other articles:

				A. Li and E. Nattie Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia J. Physiol., May 1, 2008; 586(9): 2321 - 2329. [Abstract] [Full Text] [PDF]

				S. Zanella, F. Watrin, S. Mebarek, F. Marly, M. Roussel, C. Gire, G. Diene, M. Tauber, F. Muscatelli, and G. Hilaire Necdin Plays a Role in the Serotonergic Modulation of the Mouse Respiratory Network: Implication for Prader-Willi Syndrome J. Neurosci., February 13, 2008; 28(7): 1745 - 1755. [Abstract] [Full Text] [PDF]

				M. B. Dias, T. B. Nucci, L. O. Margatho, J. Antunes-Rodrigues, L. H. Gargaglioni, and L. G. S. Branco Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2 J Appl Physiol, November 1, 2007; 103(5): 1780 - 1788. [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]

				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]