Neuropharmacologic correlates of deglutition: Lessons from fictive swallowing

Abstract

Pharmacologic investigations into the transmission processes underlying fictive swallowing in the rat have disclosed the potential diversity of chemical signals used in central deglutitive pathways. Monoaminergic mechanisms appear to serve as links between subcortical structures and the medullary pattern generator of swallowing (PGS), and may play a critical role in maintaining internal facilitatory drive, required by the PGS for optimal responsivity to peripheral sensory input. Cholinergic bulbar interneurons form an integral component of the PGS subnetwork controlling esophageal peristalsis. Local GABA neurons exert a tonic inhibition of the buccopharyngeal stage, may regulate buccopharyngeal-esophageal coupling, and may contribute to peristaltic rhythmic generation at both the premotoneuronal and motoneuronal level. Receptor subtypes for excitatory amino acids (glutamate, aspartate) are differentially associated with deglutitive premotoneurons for both the buccopharyngeal and esophageal stage, as well as with ambiguus motoneurons. Preliminary evidence suggests the existence of excitatory peptidergic mechanisms involving thyrotropin-releasing hormone, vasopressin, oxytocin, and somatostatin, a probable candidate for excitatory transmitter in the solitarioambigual internuncial projection to motoneurons innervating esophageal striated musculature. Further validation of this experimental model may ultimately help to establish a framework for the clinical recognition, management, and exploitation of drug actions on central deglutitive neuroeffectors.

Synaptic Control of Motoneuronal Excitability

“…They mediate many of the afferent or descending signals that initiate these behaviors, which include locomotion (43, 590), chewing (608), and deglutition (105). Furthermore, exogenous glutamate can activate a variety of episodic rhythmic behaviors.…”

“…GABA-and glycine-mediated postsynaptic inhibition of motoneuron activity also contributes significantly to production of rhythmic behaviors, including respiration (353,834), locomotion (201,486,644,968), chewing (207,337,538), and swallowing (105), where motoneuron activity is characterized by sequential phases of excitation and inhibition. Inhibitory synaptic control of excitability during the active phase will affect the timing of burst onset and offset (affecting onset of muscle contraction and relaxation), firing pattern, and recruitment order (961,969,1049,1377,1379).…”

Direct synaptic projections to esophageal motoneurons in the nucleus ambiguus from the nucleus of the solitary tract of the rat

“…They were all Gray's type I terminals. Since swallowing and esophageal peristalsis is produced by coordinated synchronous muscle contractions (Miller, 1982;Bieger, 1984Bieger, , 1991, our results provide anatomical bases for the notion that the NTS inputs generate synchronized discharge on the esophageal motoneurons, which exert coordinated activity of the esophageal muscles.…”

Swallowing and Stroke

“…There are multiple receptor sites within the pharynx, which bind pharmacological agents [78]. Anecdotal reports have suggested that both cisapride and nifedipine may aid those with mild-to-moderate dysphagia.…”