Vagal oxytocin receptors are necessary for esophageal motility and function

Oxytocin plays a key role in reproductive physiology but has recently garnered interest for its involvement in modulating feeding behavior. The vagus nerve contributes to feeding behavior control, as well as other gastrointestinal functions. Oxytocin receptors (OTR) are expressed on the vagus, but their role is poorly understood. Herein, we evaluated the contribution of the vagal OTR to food intake and body weight control in male and female rats. Virogenetic knockdown of vagal OTR resulted in reduced body weight and food intake in male rats. Loss of OTR in the vagus also resulted in suppressed locomotor activity in males but hyperactivity in females. Importantly, rats with vagal OTR knockdown, but not controls, exhibited a significantly elevated mortality rate starting 4 weeks after knockdown, with males being disproportionately affected. Mortality followed large eating bouts and was accompanied by abnormal presence of food in the mouth and esophagus, suggesting death by aspiration or food in the airways and suggesting a crucial role of vagal OTR in upper gastrointestinal tract motility. Furthermore, in vivo experiments revealed impaired esophageal transit. Ex vivo findings indicated oxytocin’s contribution to lower esophageal sphincter contraction. Our findings demonstrated a critical role for the oxytocin system: essential function of vagal OTR for esophageal transit and swallowing.