Hypothalamic–vagal oxytocinergic neurocircuitry modulates gastric emptying and motility following stress

Abstract

Key points Stress triggers and exacerbates the symptoms of functional gastrointestinal disorders, such as delayed gastric emptying and impaired gastric motility. Understanding the mechanisms by which the neural circuits, impaired by stress, are restored may help to identify potential targets for more effective therapeutic interventions. Oxytocin administration or release ameliorates the stress‐induced delayed gastric emptying and motility. However, is it unclear whether the effects are mediated via the hypothalamic‐pituitary‐adrenocortical axis or the oxytocinergic projections from the paraventricular nucleus of the hypothalamus to brainstem neurones of the dorsal vagal complex. We used Cre‐inducible designer receptors exclusively activated by designer drugs to demonstrate the fundamental role of the oxytocinergic hypothalamic–vagal projections in the gastric adaptation to stress. Abstract Stress triggers and exacerbates the symptoms of functional gastrointestinal (GI) disorders, such as delayed gastric emptying and impaired gastric motility. The prototypical anti‐stress hormone, oxytocin (OXT), plays a major role in the modulation of gastric emptying and motility following stress. It is not clear, however, whether the amelioration of dysregulated GI functions by OXT is mediated via an effect on the hypothalamic‐pituitary‐adrenocortical axis or the oxytocinergic projections from the paraventricular nucleus of the hypothalamus (PVN) to neurones of the dorsal vagal complex (DVC). In the present study we tested the hypothesis that the activity of hypothalamic–vagal oxytocinergic neurocircuits plays a major role in the gastric adaptation to stress. Cre‐inducible designer receptors exclusively activated by designer drugs (DREADDs) were injected into the DVC of rats and retrogradely transported to allow selective expression in OXT neurones in the PVN. Following acute stress and either chronic heterotypic (CHe) or chronic homotypic (CHo) stress, gastric emptying was assessed via the [13C]‐octanoic acid breath test, and gastric tone and motility were assessed via strain gauges sewn on the surface of the stomach. Activation of the hypothalamic–vagal oxytocinergic neurocircuitry, by DREADD agonist clozapine‐N‐oxide (CNO), prevented the delayed gastric emptying observed following acute or CHe stress, and 4th ventricular administration of CNO increased gastric tone and motility. Conversely, CNO‐mediated inhibition of the hypothalamic–vagal oxytocinergic neurocircuitry prevented the CHo‐induced adaptation in gastric emptying, and an increase in gastric tone and motility. Taken together, the data support the hypothesis that hypothalamic–vagal oxytocinergic neurocircuits play a major role in the modulation of gastric emptying and motility following stress.

Perinatal High Fat Diet Exposure Alters Oxytocin and Corticotropin Releasing Factor Inputs onto Vagal Neurocircuits Controlling Gastric Motility

“…Then, the response to repeat injection of OXT was assessed. Changes to corpus tone and motility were measured as described previously 5 . At the completion of the experiment, the rat was perfused with 0.9% saline followed by 4% PFA and the the brainstem was removed for post-hoc verification of the injection site.…”

Roles of Oxytocin in Stress Responses, Allostasis and Resilience

“…The oxytocin receptor in the dorsal motor nucleus of the vagus has been shown to reduce visceral stress responses. Activation of oxytocin neurons in the PVN projecting to the dorsal motor nucleus of the vagus has been reported to prevent the delayed gastric emptying observed following acute or chronic heterotypic stress and to increase gastric tone and motility following chronic heterotypic stress in rats [ 131 ].…”

Systematic Review of Acupuncture and Moxibustion in Colorectal Cancer Care: A Synthesis of the Evidence

“…First, both central and peripheral mechanisms may contribute to the therapeutic effects of acupuncture and moxibustion. On the one hand, the dorsal vagal complex (DVC) and the paraventricular hypothalamic nucleus (PVN) are deemed the most important nuclei that regulate GI function in the higher central nervous system (CNS) and are related to neuroendocrine and autonomic function [40,41]. Acupuncture acts on acupoints to stimulate nerves, thus promoting signal transduction.…”