Central inhibition of initiation of swallowing by systemic administration of diazepam and baclofen in anaesthetized rats

Abstract

Dysphagia is caused not only by neurological and/or structural damage but also by medication. We hypothesized memantine, dextromethorphan, diazepam, and baclofen, all commonly used drugs with central sites of action, may regulate swallowing function. Swallows were evoked by upper airway (UA)/pharyngeal distension, punctate mechanical stimulation using a von Frey filament, capsaicin or distilled water (DW) applied topically to the vocal folds, and electrical stimulation of a superior laryngeal nerve (SLN) in anesthetized rats and were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles and by visualizing laryngeal elevation. The effects of intraperitoneal or topical administration of each drug on swallowing function were studied. Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topically applied diazepam or baclofen had no effect on swallowing. These data indicate that diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. NEW & NOTEWORTHY Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topical applied diazepam or baclofen was without effect on swallowing. Diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats.