Sex Differences And Stress Alter The Vagally‐Mediated Gastric Response To Oxytocin In Rats
Authors: Zimmerman Julia E. , Jiang Yanyan , Travagli R. Alberto 
Published: June 2021

Stress and stress maladaptation play critical roles in the development of functional gastrointestinal (GI) disorders. Females have a higher incidence of functional GI disorders, likely due to fluctuations in estrogen levels, which we have shown to correlate with increased inhibitory vagal output to the GI tract. Previous studies have shown that levels of anti‐stress hormone oxytocin vary in response to stress: the more oxytocin the better the individual copes with stressful events. Furthermore, our previous studies (PMC4287746) showed that acute stress induces plastic changes in the vagally‐mediated gastric response to oxytocin, however gastric motility responses to brainstem application of oxytocin in male vs female in response to chronic stress are not yet known.

The aim of this study was to test the hypothesis that sex differences and stress alter the gastric, vagally‐mediated response to oxytocin.

SD rats were divided into the following groups 1) male, 2) low estrogen female, and 3) high estrogen female. Rats were further subdivided into the following groups: i) control, and 5 consecutive days of ii) chronic repetitive homotypic stress (these rats adapt to stress; CHo), and iii) chronic repetitive heterotypic stress (these rats do not adapt to stress; CHe). At the end of the stress load, rats were anaesthetized and strain gauges were sewn to the anterior stomach to record antrum and corpus tone and motility variation upon oxytocin microinjected in the dorsal motor nucleus of the vagus to record the changes in corpus and antrum. The postganglionic vagal pathway affected by oxytocin was investigated via i.v. injection of L‐NAME, VIP antagonist or bethanechol.

Focusing on antrum motility, but similar data were obtained with corpus tone and motility as well as antrum tone, our results suggest: i) in male rats (N=4 for all) the oxytocin induced inhibition in antral motility was attenuated significantly by L‐NAME only in controls (from 65±5% to 23±7% decrease from baseline), while in stressed animals, the response was mediated also via engagement of a VIP‐dependent pathway. ii) in all the groups from low or high estrogen females (N=3 for all), the oxytocin‐mediated gastric response was regulated via both L‐NAME (from 53±5% to 43±7% decrease from baseline, in high estrogen control) and VIP‐sensitive pathways (from 53±5 to 8±36% decrease from baseline, in high estrogen control).

In conclusion, our data indicate that females appear to respond to oxytocin to a lesser extent than males, and the vagally‐mediated pathways controlling tone and motility by females are similar to those used by stressed males. These observations may lead to a better explanation of the higher incidence of functional GI disorders in females.

Support or Funding Information

American Physiological Society, Undergraduate Summer Research Fellowship

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.