Role of bulbar serotonergic neurotransmission in the initiation of swallowing in the rat

Abstract

In rats anaesthetized with urethane and subjected to pharyngolaryngeal deafferentation, activation of central serotonin receptors was shown to evoke repetitive swallowing. Dose-response relationships were examined for the deglutitory effects of l-tryptophan, l-5-hydroxytryptophan ( l-5-HTP), quipazine (QPZ), chloro-piperazinyl-pyrazine (CPP), 5-methoxydimethyltryptamine (5-MeODMT) and tryptamine. Agonists could be grouped according to their efficacy in increasing either repetitive swallowing rate or buccopharyngeal deglutitory pressure. With respect to the former, the efficacy increased in the following order: 5-MeODMT, l-tryptophan < tryptamine, l-5-HTP < QPZ < CPP; with respect to the latter, it decreased in the order: 5-MeODMT, QPZ > l-5-HTP, l-tryptophan > tryptamine, CPP. The stimulatory effects on the swallowing rate were inhibited by methysergide, metergoline and d-lysergic acid diethylamide (LSD). The persistence of these effects after decerebration and their elicitation, upon close-arterial and topical drug administration to the fourth ventricle, implicate the rhombencephalon as the major locus of action. Serotonin agonists enhanced reflex deglutition elicited by electrical stimulation of the superior laryngeal nerve or the solitary tract. Antagonists blocked the facilitation of reflex swallowing at the same dose levels at which they abolished agonist-evoked swallowing; however, they failed to diminish maximal reflex responses. The data support the hypothesis that the neural substrate of serotonergically-evoked, “automatic” swallowing is organized within the rhombencephalon and operates to set a facilitatory bias for deglutitory internuncial neurones as well as effector motoneurones.