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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% O 2 -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-HT 2 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% O 2 ) 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-HT 2 receptors and that the CIH effect on LTF requires non-5-HT 2 serotonin receptors, probably 5-HT 6 and/or 5-HT 7 subtype(s). respiratory control; plasticity; 5-HT antagonists Address for reprint requests and other correspondence: L. Ling, Division of Sleep Medicine@BIDMC , Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115 (E-mail: lling@partners.org ).
AJP - Regulatory, Integrative and Comparative Physiology – The American Physiological Society
Published: Feb 1, 2004
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