Origin of respiratory activities in the medullary raphe nuclei of rats

Pharmacological neuromodulation of swallowing may represent a promising therapeutic option to treat dysphagia. Previous studies suggested a serotonergic control of swallowing, but mechanisms remain poorly understood. Here, we investigated the effects of the serotonergic agonist quipazine on swallowing, using the arterially perfused working heart-brainstem (in situ) preparation in rats. Systemic injection of quipazine produced single swallows with motor patterns and swallow-breathing coordination similar to spontaneous swallows, and increased swallow rate with moderate changes in cardiorespiratory functions. Methysergide, a 5-HT2 receptor antagonist, blocked the excitatory effect of quipazine on swallowing, but had no effect on spontaneous swallow rate. Microinjections of quipazine in the nucleus of the solitary tract were without effect. In contrast, similar injections in caudal medullary raphe nuclei increased swallow rate without changes in cardiorespiratory parameters. Thus, quipazine may exert an excitatory effect on raphe neurons via stimulation of 5-HT2A receptors, leading to increased excitability of the swallowing network. In conclusion, we suggest that pharmacological stimulation of swallowing by quipazine in situ represents a valuable model for experimental studies. This work paves the way for future investigations on brainstem serotonergic modulation, and further identification of neural populations and mechanisms involved in swallowing and/or swallow-breathing interaction.

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Powerful depressor and sympathoinhibitory effects evoked from neurons in the caudal raphe pallidus and obscurus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.5.r1295 ◽

1995 ◽

Vol 268 (5) ◽

pp. R1295-R1302 ◽

Cited By ~ 14

Author(s):

M. J. Coleman ◽

R. A. Dampney

Keyword(s):

Arterial Pressure ◽

Sympathetic Activity ◽

Raphe Nuclei ◽

Ventrolateral Medulla ◽

Gamma Aminobutyric Acid ◽

Medullary Raphe ◽

Dose Dependent Decrease ◽

Raphé Nuclei ◽

Raphe Pallidus ◽

Dose Dependent

Microinjection of glutamate into sites within the medullary raphe nuclei (pallidus and obscurus) at levels caudal to the obex resulted in a dose-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate in anesthetized rabbits. The depressor and sympathoinhibitory responses were similar in magnitude to those elicited from the previously described depressor region in the caudal ventrolateral medulla (CVLM) but had a shorter duration, in both intact and barodenervated animals. The bradycardia was not altered by barodenervation but was reduced after administration of propranolol or atropine and abolished after administration of both drugs. The neuroinhibitory compounds gamma-aminobutyric acid or muscimol had no effect on MAP or RSNA when injected into the caudal medullary raphe nuclei but evoked a pressor and sympathoexcitatory response when injected into the CVLM. The results indicate that neurons within the caudal raphe pallidus and obscurus can powerfully inhibit sympathetic activity, but unlike sympathoinhibitory neurons in the CVLM, they are not tonically active and are not capable of producing sustained changes in arterial pressure and sympathetic activity.

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Stimulation of the rat medullary raphe nuclei induces differential responses in respiratory muscle activity

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2008.12.004 ◽

2009 ◽

Vol 165 (2-3) ◽

pp. 208-214 ◽

Cited By ~ 13

Author(s):

S. Besnard ◽

P. Denise ◽

B. Cappelin ◽

M. Dutschmann ◽

C. Gestreau

Keyword(s):

Muscle Activity ◽

Respiratory Muscle ◽

Raphe Nuclei ◽

Medullary Raphe ◽

Differential Responses ◽

Raphé Nuclei ◽

Respiratory Muscle Activity ◽

Stimulation Of

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Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00317.2017 ◽

2018 ◽

Vol 314 (3) ◽

pp. G341-G348 ◽

Cited By ~ 5

Author(s):

Hiroyuki Nakamori ◽

Kiyotada Naitou ◽

Yuuki Horii ◽

Hiroki Shimaoka ◽

Kazuhiro Horii ◽

...

Keyword(s):

Spinal Cord ◽

Electrical Stimulation ◽

Raphe Nuclei ◽

Lumbosacral Spinal Cord ◽

Pelvic Nerves ◽

Medullary Raphe ◽

Raphé Nuclei ◽

Type 3 ◽

Stimulation Of

Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal motility. Because spinal 5-HT is derived from neurons of the medullary raphe nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats. Electrical stimulation of the medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic neurons can be simultaneously activated by the raphe stimulation and released GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation center, a GABAA receptor antagonist was preinjected intrathecally to manifest excitatory responses. When spinal GABAA receptors were blocked by the antagonist, electrical stimulation of the medullary raphe nuclei increased colorectal contractions. This effect of the raphe nuclei was inhibited by intrathecal injection of 5-hydroxytryptamine type 2 (5-HT2) and type 3 (5-HT3) receptor antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of colorectal motility. Transection of the pelvic nerves, but not transection of the colonic nerves, prevented the effect of the raphe nuclei on colorectal motility. These results demonstrate that activation of the medullary raphe nuclei causes augmented contractions of the colorectum via 5-HT2 and 5-HT3 receptors in the lumbosacral defecation center. NEW & NOTEWORTHY We have shown that electrical stimulation of the medullary raphe nuclei causes augmented contractions of the colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on colorectal motility is exerted through activation of 5-hydroxytryptamine type 2 and type 3 receptors in the lumbosacral defecation center. The descending serotoninergic raphespinal tract represents new potential therapeutic targets against colorectal dysmotility such as irritable bowel syndrome.

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