Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing.
We tested the hypothesis that chronic intermittent hypoxia (CIH) elicits plasticity in the central neural control of breathing via serotonin-dependent effects on the integration of carotid chemoafferent inputs. Adult rats were exposed to 1 week of nocturnal CIH (11-12% O(2)/air at 5 min intervals; 12 hr/night). CIH and untreated rats were then anesthetized, paralyzed, vagotomized, and artificially ventilated. Time-dependent hypoxic responses were assessed in the phrenic neurogram during and after three 5 min episodes of isocapnic hypoxia. Integrated phrenic amplitude (integralPhr) responses during hypoxia were greater after CIH at arterial oxygen pressures (PaO(2)) between 25 and 45 mmHg (p < 0.05), but not at higher PaO(2) levels. CIH did not affect hypoxic phrenic burst frequency responses, although the post-hypoxia frequency decline that is typical in rats was abolished. integralPhr and frequency responses to electrical stimulation of the carotid sinus nerve were enhanced by CIH (p < 0.05). Serotonin-dependent long-term facilitation (LTF) of integralPhr was enhanced after CIH at 15, 30, and 60 min after episodic hypoxia (p < 0.05). Pretreatment with the serotonin receptor antagonists methysergide (4 mg/kg, i.v.) and ketanserin (2 mg/kg, i.v.) reversed CIH-induced augmentation of the short-term hypoxic phrenic response and restored the post-hypoxia frequency decline in CIH rats. Whereas methysergide abolished CIH-enhanced phrenic LTF, the selective 5-HT(2) antagonist ketanserin only partially reversed this effect. The results suggest that CIH elicits unique forms of serotonin-dependent plasticity in the central neural control of breathing. Enhanced LTF after CIH may involve an upregulation of a non-5-HT(2) serotonin receptor subtype or subtypes.
Ling
L
L
Departments of Comparative Biosciences and Preventive Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA.
Fuller
D D
DD
Bach
K B
KB
Kinkead
R
R
Olson
E B
EB
Mitchell
G S
GS
D000818:Animals; D001049:Apnea / Q000503:physiopathology; D001158:Arteries; D001273:Atmosphere Exposure Chambers; D001784:Blood Gas Analysis; D002346:Carotid Sinus / Q000294:innervation / Q000503:physiopathology; D002490:Central Nervous System / Q000503:physiopathology*; D002908:Chronic Disease; D004558:Electric Stimulation; D000860:Hypoxia / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D009046:Motor Neurons; D009409:Nerve Crush; D009473:Neuronal Plasticity / Q000187:drug effects; D010791:Phrenic Nerve / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D012684:Sensory Thresholds; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014628:Vagotomy
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin