Quipazine Elicits Swallowing in the Arterially Perfused Rat Preparation: A Role for Medullary Raphe Nuclei?

Victor Bergé-Laval,Christian Gestreau

doi:10.3390/ijms21145120

Abstract

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.

Highlights

Despite extensive experimental and clinical studies, swallowing remains one of the most important and least appreciated functions [1]
Mean group data showed that systemic injection of QPZ (1.5 μM/kg) significantly increased respiratory frequency (Rf) (23 ± 9 vs. 30 ± 17 cycles/min, in control vs. QPZ groups, respectively; p < 0.05; Table S1)
This study demonstrated that the serotonergic agonist QPZ enhanced swallowing in situ

Summary

Introduction

Despite extensive experimental and clinical studies, swallowing remains one of the most important and least appreciated functions [1]. Dysfunctions in the brainstem’s swallowing central pattern generator (swCPG) and other medullary or supra-medullary structures may be an important causal factor of oropharyngeal dysphagia, a severe disease whose neural pathophysiology remains poorly understood [2,3,4]. The precise neural mechanisms operated by the swCPG are obscure, and the interactions between the central pattern generator for breathing (rCPG) and the swCPG are not fully characterized [7,8]. This lack of knowledge may be explained by the complexity of brainstem circuitry, the paucity of information on the phenotypes of the swCPG neurons and their mechanisms of neuromodulation. The experimental protocols and/or animal models required to study swallowing and swallow-breathing coordination are generally complex, time-consuming and expensive [8,9,10,11]

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