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

This Article Full Text Full Text (PDF) All Versions of this Article: 286/2/R334    most recent 00463.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in 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 Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by McGuire, M. Articles by Ling, L. Search for Related Content PubMed PubMed Citation Articles by McGuire, M. Articles by Ling, L.

CARDIAC, RENAL, AND RESPIRATORY INTEGRATION

Serotonin receptor subtypes required for ventilatory long-term facilitation and its enhancement after chronic intermittent hypoxia in awake rats

Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Submitted 14 August 2003 ; accepted in final form 6 October 2003

Respiratory long-term facilitation (LTF), a serotonin-dependent, persistent augmentation of respiratory activity after episodic hypoxia, is enhanced by pretreatment of chronic intermittent hypoxia (CIH; 5 min 11-12% O₂-5 min air, 12 h/night for 7 nights). The present study examined the effects of methysergide (serotonin 5-HT_1,2,5,6,7 receptor antagonist), ketanserin (5-HT₂ antagonist), or clozapine (5-HT_2,6,7 antagonist) on both ventilatory LTF and the CIH effect on ventilatory LTF in conscious male adult rats to determine which specific receptor subtype(s) is involved. In untreated rats (i.e., animals not exposed to CIH), LTF, induced by five episodes of 5-min poikilocapnic hypoxia (10% O₂) separated by 5-min normoxic intervals, was measured twice by plethysmography. Thus the measurement was conducted 1-2 days before (as control) and 1 h after systemic injection of methysergide (1 mg/kg ip), ketanserin (1 mg/kg), or clozapine (1.5 mg/kg). Resting ventilation, metabolic rate, and hypoxic ventilatory response (HVR) were unchanged, but LTF (18% above baseline) was eliminated by each drug. In CIH-treated rats, LTF was also measured twice, before and 8 h after CIH. Vehicle, methysergide, ketanserin, or clozapine was injected 1 h before the second measurement. Neither resting ventilation nor metabolic rate was changed after CIH and/or any drug. HVR was unchanged after methysergide and ketanserin but reduced in four of seven clozapine rats. The CIH-enhanced LTF (28%) was abolished by methysergide and clozapine but only attenuated by ketanserin (to 10%). Collectively, these data suggest that ventilatory LTF requires 5-HT₂ receptors and that the CIH effect on LTF requires non-5-HT₂ serotonin receptors, probably 5-HT₆ and/or 5-HT₇ subtype(s).

respiratory control; plasticity; 5-HT antagonists

This article has been cited by other articles:

				M. Kanamaru and I. Homma Dorsomedial medullary 5-HT2 receptors mediate immediate onset of initial hyperventilation, airway dilation, and ventilatory decline during hypoxia in mice Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2009; 297(1): R34 - R41. [Abstract] [Full Text] [PDF]

				K. Ptak, T. Yamanishi, J. Aungst, L. S. Milescu, R. Zhang, G. B. Richerson, and J. C. Smith Raphe Neurons Stimulate Respiratory Circuit Activity by Multiple Mechanisms via Endogenously Released Serotonin and Substance P J. Neurosci., March 25, 2009; 29(12): 3720 - 3737. [Abstract] [Full Text] [PDF]

				J. H. Mateika and G. Narwani Intermittent hypoxia and respiratory plasticity in humans and other animals: does exposure to intermittent hypoxia promote or mitigate sleep apnoea? Exp Physiol, March 1, 2009; 94(3): 279 - 296. [Abstract] [Full Text] [PDF]

				M. McGuire, J. L. Tartar, Y. Cao, R. W. McCarley, D. P. White, R. E. Strecker, and L. Ling Sleep fragmentation impairs ventilatory long-term facilitation via adenosine A1 receptors J. Physiol., November 1, 2008; 586(21): 5215 - 5229. [Abstract] [Full Text] [PDF]

				M. McGuire, C. Liu, Y. Cao, and L. Ling Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA receptors in awake rats J Appl Physiol, September 1, 2008; 105(3): 942 - 950. [Abstract] [Full Text] [PDF]

				A. Tadjalli, J. Duffin, Y. M. Li, H. Hong, and J. Peever Inspiratory activation is not required for episodic hypoxia-induced respiratory long-term facilitation in postnatal rats J. Physiol., December 1, 2007; 585(2): 593 - 606. [Abstract] [Full Text] [PDF]

				A. A. Varney and E. H. Schlenker Thyroid status affects 5-HT2A receptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R2070 - R2080. [Abstract] [Full Text] [PDF]

				S. Mahamed and G. S. Mitchell Sleep Apnoea & Hypertension: Physiological bases for a causal relation: Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea? Exp Physiol, January 1, 2007; 92(1): 27 - 37. [Abstract] [Full Text] [PDF]

				T. E. Dick, Y.-H. Hsieh, N. Wang, and N. Prabhakar Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat Exp Physiol, January 1, 2007; 92(1): 87 - 97. [Abstract] [Full Text] [PDF]

				M. McGuire and L. Ling Ventilatory long-term facilitation is greater in 1- vs. 2-mo-old awake rats J Appl Physiol, April 1, 2005; 98(4): 1195 - 1201. [Abstract] [Full Text] [PDF]

				F. J. Golder and G. S. Mitchell Spinal Synaptic Enhancement with Acute Intermittent Hypoxia Improves Respiratory Function after Chronic Cervical Spinal Cord Injury J. Neurosci., March 16, 2005; 25(11): 2925 - 2932. [Abstract] [Full Text] [PDF]