The 5‐HT_1A Agonist 8‐OH‐DPAT Enhances Submental Laryngeal Elevator EMG Amplitude During Swallow

Abstract

Swallow is a critical behavior for sustaining life, important for both for the ingestion of nutrients and for protecting the airways. To produce an effective swallow, neural circuits must coordinate over 20 muscles across multiple cranial/spinal nerves to produce a rostral‐caudal pressure gradient to move the bolus from the mouth to the stomach. The medullary raphe nuclei are the main source of serotonin in the brainstem, and this region has been implicated in modulation of swallow and other airway protective behaviors. In order to explore the role of serotonin in swallow, we conducted experiments in adult cats (n = 6). Animals were anesthetized with intravenous sodium pentobarbital and tracheostomized. Fine wire intramuscular electromyograms (EMGs) were recorded from swallow and respiratory related muscles. The 5‐HT1A receptor agonist 8‐OH‐DPAT was delivered either intravenously through the femoral artery (n = 3) or intra‐arterially through the vertebral artery (n = 3) as a series of six cumulative doses (0.1‐30 ug/kg i.v.; 1‐300 ug/kg i.a.). Swallow was elicited by oral infusion water (3 ml) via syringe and was confirmed by the presence coordinated activity on swallow‐related EMGs. EMG amplitude was normalized prior to analysis. Administration of 8‐OH‐DPAT demonstrated a significant effect on the two primary submental muscles responsible for hyolaryngeal elevation necessary for full occlusion of the airway by the epiglottis. Mylohyoid amplitude increased by 45% (p = 0.006) and geniohyoid amplitude increased by 64% (p = 0.04) at the highest dose when compared to control. This is evidence of the raphe and its serotonergic network coordinating distributed aspects of the swallow control network as these two muscles are innervated via separate cranial nerves: the trigeminal for the mylohyoid and hypoglossal for the geniohyoid. Disordered hyolaryngeal function is a leading cause of aspiration across a multitude of neuro‐ degenerative and ‐traumatic diseases, and pharmacologic intervention with serotonergic agonists represents a promising agent for therapeutic interventions.