Methysergide augments the acute, but not the sustained, hypoxic ventilatory response in goats

Herman, Jay K.; O’Halloran, Ken D.; Mitchell, Gordon S.; Bisgard, G. E.

doi:10.1016/s0034-5687(99)00070-5

Cited by 16 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An additional distinction between CIH and sustained hypoxia is that ventilatory acclimatization to sustained hypoxia is insensitive to serotonin depletion (Olson, 1987) or methysergide pretreatment (Herman et al, 1999), whereas serotonin receptor antagonists attenuate CIH-induced plasticity (this study). Thus, our results suggest that chronic intermittent hypoxia increases the capacity for central serotonergic modulation, whereas chronic sustained hypoxia acts primarily by nonserotonergic, peripheral chemoreceptor mechanisms.…”

Section: Sustained Versus Intermittent Hypoxiamentioning

confidence: 82%

Chronic Intermittent Hypoxia Elicits Serotonin-Dependent Plasticity in the Central Neural Control of Breathing

Ling

Fuller²,

Kb³

et al. 2001

J. Neurosci.

Self Cite

240

265

View full text Add to dashboard Cite

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 (͐Phr) responses during hypoxia were greater after CIH at arterial oxygen pressures (PaO 2 ) between 25 and 45 mmHg ( p Ͻ 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. ͐Phr and frequency responses to electrical stimulation of the carotid sinus nerve were enhanced by CIH ( p Ͻ 0.05). Serotonin-dependent long-term facilitation (LTF) of ͐Phr was enhanced after CIH at 15, 30, and 60 min after episodic hypoxia ( p Ͻ 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 posthypoxia 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 serotonindependent 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. Key words: control of breathing; serotonin; plasticity; hypoxia; phrenic motoneurons; ratsAlthough plasticity is a fundamental property of neural systems (Zigmond et al., 1999;Kandel et al., 2000), its significance in the central neural control of breathing in adult mammals has been appreciated only recently (Eldridge and Millhorn, 1986;Mitchell et al., 1990Mitchell et al., , 1993McCrimmon et al., 1995; Poon, 1996a,b;Powell et al., 1998). In this study, we demonstrate the existence of novel forms of serotonin-dependent plasticity in the hypoxic ventilatory control system elicited by chronic intermittent hypoxia.The hypoxic ventilatory response in mammals consists of several time-dependent facilitatory and inhibitory mechanisms that are revealed by different patterns and durations of hypoxia (Bisgard and Neubauer, 1995;Powell et al., 1998). In anesthetized rats, a single 5 min hypoxic episode increases phrenic nerve activity, an effect known as the short-term hypoxic phrenic response. When normoxia is restored, phrenic burst frequency decreases below the original baseline level and returns to baseline over several minutes (post-hypoxia frequency decline) (Coles and Dick, 1996;Bach et al., 1999).A unique form of serotonin-dependent respiratory plasticity, known as phrenic long-term facilitatio...

show abstract

Section: Sustained Versus Intermittent Hypoxiamentioning

confidence: 82%

Chronic Intermittent Hypoxia Elicits Serotonin-Dependent Plasticity in the Central Neural Control of Breathing

Ling

Fuller²,

Kb³

et al. 2001

J. Neurosci.

Self Cite

240

265

View full text Add to dashboard Cite

show abstract

“…In accordance with this notion, Kirby & McQueen (1984) showed that 5-HT 2A/2C receptors contribute to the inhibition of carotid body activity, whereas methysergide (antagonist 5-HT 2A/2C ) administration was reported to augment the acute hypoxic ventilatory response, acting on tidal volume (Herman et al 1999). Although this result suggests that 5-HT 2 in the NRM does not participate in the hypoxia-induced hyperventilation, its role in respiratory responses to hypoxia is still a subject of debate.…”

Section: Ventilatory Response To Hypoxiamentioning

confidence: 87%

“…In general, animals respond to hypoxia by reducing body temperature (T b , anapyrexia), metabolic rate and increasing ventilation (Gellhorn & Janus 1936, Cross et al 1958, Miller & Miller 1966, Sim & Joseph 1991, Wood 1991, Wood & Malvin 1991, Herman et al 1999. At first sight, these responses appear to occur in opposite directions, i.e.…”

mentioning

confidence: 99%

5‐HT_1A, but not 5‐HT₂ and 5‐HT₇, receptors in the nucleus raphe magnus modulate hypoxia‐induced hyperpnoea

2008

View full text Add to dashboard Cite

show abstract

“…Central mechanisms contribute to a decline in ventilation in parallel with peripheral chemoreceptor activation; if the initial hyperventilation fails to restore sufficient PO 2 in arterial blood, the central mechanisms reduce the metabolic demand of the respiratory musculature by lowering ventilation (Neubauer et al, 1990; Carroll and Agarwal, 2010; Teppema and Dahan, 2010). Various mechanisms underlying the hypoxic decline in ventilation have been proposed including: ( i ) hyperperfusion of medullary CO 2 -sensitive areas (Neubauer et al, 1990); ( ii ) hypometabolism leading to a drop in CO 2 production (Mortola, 2004); ( iii ) release of neuromodulators such as adenosine (Runold et al, 1989; Neubauer et al, 1990; Kawai et al, 1995) or serotonin (5-HT) (Herman et al, 1999; Richter et al, 1999); and ( iv ) intrinsic activation of cells in the medulla oblonga by low PO 2 (Nolan and Waldrop, 1993; Bodineau et al, 2001; Voituron et al, 2006, 2011). …”

Section: Introductionmentioning

confidence: 99%

Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants

et al. 2016

View full text Add to dashboard Cite

We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, raphe magnus nucleus, lateral, and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas ~45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labeled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labeled for serotonin in the raphe magnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labeled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by (i) the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, (ii) the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and (iii) the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modeling the breathing network of premature infants.

show abstract

Methysergide augments the acute, but not the sustained, hypoxic ventilatory response in goats

Cited by 16 publications

References 26 publications

Chronic Intermittent Hypoxia Elicits Serotonin-Dependent Plasticity in the Central Neural Control of Breathing

Chronic Intermittent Hypoxia Elicits Serotonin-Dependent Plasticity in the Central Neural Control of Breathing

5‐HT_1A, but not 5‐HT₂ and 5‐HT₇, receptors in the nucleus raphe magnus modulate hypoxia‐induced hyperpnoea

Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants

Contact Info

Product

Resources

About

Methysergide augments the acute, but not the sustained, hypoxic ventilatory response in goats

Cited by 16 publications

References 26 publications

Chronic Intermittent Hypoxia Elicits Serotonin-Dependent Plasticity in the Central Neural Control of Breathing

Chronic Intermittent Hypoxia Elicits Serotonin-Dependent Plasticity in the Central Neural Control of Breathing

5‐HT1A, but not 5‐HT2 and 5‐HT7, receptors in the nucleus raphe magnus modulate hypoxia‐induced hyperpnoea

Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants

Contact Info

Product

Resources

About

5‐HT_1A, but not 5‐HT₂ and 5‐HT₇, receptors in the nucleus raphe magnus modulate hypoxia‐induced hyperpnoea