Serotonin and the control of ventilation in awake rats.

Olson, E. B.; Dempsey, Jerome A.; McCrimmon, Donald R.

doi:10.1172/jci109510

Cited by 66 publications

(34 citation statements)

References 13 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pharmacological studies have demonstrated that selective depletion of 5-HT in the central nervous system of cats and rats by parenteral administration of 5-HT enzyme inhibitors or neurotoxins results in increased ventilation (Florez, Delgado & Aronijo, 1972;Olsen et al 1979). On the other hand, administration of relatively specific 5-HT receptor agonists or precursors of 5-HT depresses phrenic nerve activity (Lalley, 1982;McCrimmon & Lalley, 1982) and ventilation (Armigo & Florez, 1974;Lambert, Friedman, Buchweitz & Gershon, 1978;Lundberg, Mueller & Breese, 1980).…”

Section: Discussionmentioning

confidence: 99%

“…PCA is taken up into serotoninergic nerve terminals where it rapidly evokes the release of 5-HT (Wong, Horng & Fuller, 1973;Lucot, Horowitz & Seider, 1981), resulting in serotoninergic effects which occur within several minutes. After 24 h, 5-HT terminals are depleted and in the rat this is accompanied by hyperventilation (Olson, Dempsey & McCrimmon, 1979). Fig 3 illustrates the inhibition of phrenic nerve activity (B) which occurs just after injection of PCA, which is assumed to be related to 5-HT release in the central nervous system.…”

Section: Responses To P-chloroamphetaminementioning

confidence: 99%

See 1 more Smart Citation

Serotoninergic and non‐serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.

Lalley¹

1986

The Journal of Physiology

119

View full text Add to dashboard Cite

SUMMARY1. Experiments were conducted on anaesthetized, paralysed and artificially ventilated cats in order to determine if the altered discharge pattern of phrenic motoneurones recorded during stimulation of medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus), raphe pallidus (r. pallidus)) are related to release of serotonin (5-hydroxytryptamine, 5-HT) at synapses on respiratory neurones. Effects of 5-HT released by the neurotoxinp-chloroamphetamine (PCA) on spontaneous activity of phrenic motoneurones were also examined. In addition, responses of phrenic motoneurones to 5-HT applied by micro-electrophoresis were recorded.2. Stimulation (100 Hz) of r. magnus or r. obscurus depressed the spontaneous inspiratory discharges ofphrenic motoneurones. Administration of the 5-HT receptor antagonists cinanserin, methysergide or methergoline reduced, but did not abolish, the inhibition. Inhibition of the neuronal reuptake of 5-HT with fluoxetine enhanced the inhibition and reduced the peak inspiratory action potential frequency of spontaneous discharges.3. Stimulation (100 Hz) of r. pallidus produced increased firing of phrenic motoneurones. Firing of phrenic motoneurones was evoked even during the normally quiescent expiratory phase of spontaneous respiratory activity. Antagonists at 5-HT receptors reduced the degree of tonic firing, resulting in partial restoration of expiratory pauses during r. pallidus stimulation. Inhibition of 5-HT reuptake, on the other hand, resulted in increased tonic firing.4. Release of 5-HT by PCA produced a rapid and severe reduction of phrenic nerve activity. Activity was restored by 5-HT receptor antagonists.5. In reserpine-treated cats, effects of stimulating medullary raphe nuclei were still pronounced, however 5-HT receptor antagonists had no effect on the responses. These results, along with the observation that 5-HT receptor antagonists are only partially effective in non-reserpinized cats, indicate that non-serotoninergic influences contribute as well to the responses evoked by raphe stimulation.6. Micro-electrophoretic application of 5-HT by large ejecting currents (100-200 nA) had weak stimulatory effects on twenty of forty-five phrenic motoneurones, which exhibited small increases in peak inspiratory discharge frequency during 5-HT application. Ejecting currents less than 100 nA were without effect. It is concluded that 5-HT analogues and agents which release endogenous 5-HT after P. M. LALLEY parenteral administration do not act directly at synapses on the soma membranes of phrenic motoneurones.7. y-Aminobutyric acid (GABA) and glycine applied by micro-electrophoresis produced rapid and marked depressant actions on phrenic motoneurones. However, intravenous administration of bicuculline (50-500 ,g/kg), a post-synaptic GABA receptor antagonist, or strychnine /sg/kg), an antagonist at glycine receptors, did not antagonize the responses to medullary raphe stimulation. Therefore, the non-serotoninergic inhibitory effects of raphe stimulation do not appear t...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Responses To P-chloroamphetaminementioning

confidence: 99%

Serotoninergic and non‐serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.

Lalley¹

1986

The Journal of Physiology

119

View full text Add to dashboard Cite

show abstract

“…However, these approaches have been difficult to interpret, and in some cases have produced contradictory results. For example, PCPA induces a substantial increase in baseline ventilation, but has no effect on the HCVRleading to the conclusion that 5-HT inhibits breathing at rest (Olson et al, 1979;Mitchell et al, 1983;Annerbrink et al, 2003). However, 5,7-DHT induces hypoventilation at rest (Olson et al, 1979) and during hypercapnia (Mueller et al, 1984), leading to the opposite conclusion -that 5-HT stimulates breathing at rest and during hypercapnia.…”

Section: Role Of Central 5-ht Neurons In Respiratory Controlmentioning

confidence: 99%

“…However, there are data that suggest that 5-HT can inhibit breathing. For example, pharmacologically depleting 5-HT with 6-fluorotryptophan or parachlorophenyalanine (PCPA) increases ventilation, and the PCPA effect partially reverses with 5-HT repletion by L-tryptophan (Olson et al, 1979). There is also evidence that respiratory output, and some respiratory neurons, can be inhibited in vivo by 5-HT under some conditions (Lalley, 1986).…”

Section: Introductionmentioning

confidence: 99%

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

Hodges¹,

Tattersall²,

Harris³

et al. 2008

J. Neurosci.

291

348

View full text Add to dashboard Cite

f/f/p mice was decreased by 50% compared with wild-type mice, whereas baseline ventilation and the hypoxic ventilatory response were normal. In addition, Lmx1b f/f/p mice rapidly became hypothermic when exposed to an ambient temperature of 4°C, decreasing core temperature to 30°C within 120 min. This failure of thermoregulation was caused by impaired shivering and nonshivering thermogenesis, whereas thermosensory perception and heat conservation were normal. Finally, intracerebroventricular infusion of 5-HT stimulated baseline ventilation, and rescued the blunted hypercapnic ventilatory response. These data identify a previously unrecognized role of 5-HT neurons in the CO 2 chemoreflex, whereby they enhance the response of the rest of the respiratory network to CO 2 . We conclude that the proper function of the 5-HT system is particularly important under conditions of environmental stress and contributes significantly to the hypercapnic ventilatory response and thermoregulatory cold defense.

show abstract

“…1–3 In the pulmonary system, serotonin affects both breathing and regulating respiratory drive. 4,5 Serotonin has been shown to play a major role in many gastrointestinal disorders such as irritable bowel syndrome, nausea, and diarrhea. 6–8 While nearly 95% of the body’s serotonin is localized in the gut, one of the more widely studied roles of serotonin is its function within the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Pharmacophore Comparison and Development of Recently Discovered Long Chain Arylpiperazine and Sulfonamide Based 5-HT7 Ligands

Rague

Tidgewell

2018

MRMC

View full text Add to dashboard Cite

The serotonin system exerts its effects on the CNS and many peripheral systems. Of the 14 serotonin receptors, the 5-HT7 receptor is the most recently discovered. The 5-HT7 receptor has been shown to be involved in stress reduction, depression, and nociceptive control. Despite the 20 years since the discovery of 5-HT7R, there are still few truly selective ligands. Two of the common scaffolds for 5-HT7R ligands are long chain arylpiperazines (LCAPs) and sulfonamide containing compounds. This review focuses on recently developed (2014–2016) 5-HT7R ligands, their selectivity for the receptor, and suggests possible new pharmacophore models for these ligands.

show abstract

Serotonin and the control of ventilation in awake rats.

Cited by 66 publications

References 13 publications

Serotoninergic and non‐serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.

Serotoninergic and non‐serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

Pharmacophore Comparison and Development of Recently Discovered Long Chain Arylpiperazine and Sulfonamide Based 5-HT7 Ligands

Contact Info

Product

Resources

About