The laryngeal adductor reflex (LAR) is modulated by the serotonin 5‐HT_1A agonist 8‐OH‐DPAT

Abstract

Airway protection is maintained through a constellation of behaviors. The laryngeal adductor reflex (LAR) responds to mechanical or chemical stimulation of the laryngeal orifice with rapid adduction of the vocal folds. While there are abundant serotonin receptors on laryngeal motoneurons, the effects of serotonin agents on the LAR have not been investigated. To this end, a dose response protocol of 8‐OH‐DPAT (5HT1A receptor agonist) was performed on adult cats (n = 2). Animals were anesthetized using an intravenous dose of sodium pentobarbital and then tracheostomized. Electromyogram (EMG) activity of laryngeal muscles was recorded and LARs were induced by infusing water into the larynx during both normocapnia (0% CO2) and hypercapnia (10% CO2) conditions. A series of six cumulative doses (1 – 300 μg/kg) were delivered intra‐venously. 8‐OH‐DPAT is thought to activate the serotonergic raphe neuron autoreceptors at lower doses and the post‐synaptic receptors on target neurons at higher doses. LAR occurred as a response to water stimulus in 50±23% of control trials. LAR occurrence was modulated by 8‐OH‐DPAT in a dose‐dependent manner: LAR frequency at lower doses may have decreased but this was variable, and LAR frequency appeared to be increased at higher doses (LAR occurred in 13±18%, 17±23%, 50±70%, 57±9%, 84±7%, and 60±4% of stimulus trials at 1, 3, 10, 30, 100, and 300 μg/kg doses, respectively). LAR can be used as a strong clinical predictor of swallow impairment; while other airway protective behaviors require activity across multiple cranial nerves, the LAR is regulated by only laryngeal branches of the vagus nerve. Thus, the LAR is a promising biomarker for testing novel therapeutic agents. These results suggest that pharmacological interventions may be capable of facilitating laryngeal function in patients suffering from dysphagia.