title: Acute intermittent hypoxia induces phrenic long-term facilitation which is modulated by 5-HT1A receptor in the caudal raphe region of the rat.
abstract: Obstructive sleep apnoea (OSA) is characterized by periods of upper airway collapse accompanied by repeated episodes of hypoxia. In experimental animals repeated bouts of hypoxia may evoke sustained augmentation of phrenic nerve activity, known as phrenic long-term facilitation (pLTF). This form of physiological compensation might contribute to stable breathing, minimizing the occurrence of apnoeas and/or hypopnoeas during sleep in patients with OSA. Serotonin (5-HT) has been shown to modulate respiratory neuronal activity, possibly via projections originating in the raphe nuclei. Our model focuses on the effects of 5-HT1A receptors blockade by selective antagonist WAY-100635 into the caudal raphe region on phrenic long-term facilitation after exposure to acute intermittent hypoxia (AIH) episodes. Adult, male, urethane-anaesthetized, vagotomized, paralyzed and mechanically ventilated Sprague-Dawley rats were exposed to AIH protocol. Experimental group received microinjection of WAY-100635 into the caudal raphe nucleus, whereas the control group received saline into the same site. Peak phrenic nerve activity and respiratory rhythm parameters were analysed during five hypoxic episodes, as well as at 15, 30 and 60 min after the end of hypoxias. In the control group, 1 h post-hypoxia pLTF was developed. Microinjections of selective 5-HT1A receptor antagonist WAY-100635 into the raphe nuclei prior to the AIH protocol prevented induction of pLTF. These results suggest that 5-HT1A receptor activation at supraspinal level is important for induction of pLTF, which is suggested to be an important respiratory neuroplasticity model in animal studies that possibly correlates with OSA in humans.
authors: Department of Neuroscience, University of Split School of Medicine, Split, Croatia.
authors: Ivana
authors: I
authors: Pavlinac Dodig
authors: Renata
authors: R
authors: Pecotic
authors: Maja
authors: M
authors: Valic
authors: Zoran
authors: Z
authors: Dogas
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008845:Microinjections / Q000379:methods; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology
chemical_list: D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide