Stress-induced neuroplasticity in the gastric response to brainstem oxytocin in male rats

Previous studies have shown that pharmacological manipulations with stress-related hormones such as corticotropin-releasing factor and thyrotropin-releasing hormone induce neuroplasticity in brainstem vagal neurocircuits, which modulate gastric tone and motility. The prototypical antistress hormone oxytocin (OXT) has been shown to modulate gastric tone and motility via vagal pathways, and descending hypothalamic oxytocinergic inputs play a major role in the vagally dependent gastric-related adaptations to stress. The aim of this study was to investigate the possible cellular mechanisms through which OXT modulates central vagal brainstem and peripheral enteric neurocircuits of male Sprague-Dawley rats in response to chronic repetitive stress. After chronic (5 consecutive days) of homotypic or heterotypic stress load, the response to exogenous brainstem administration of OXT was examined using whole cell patch-clamp recordings from gastric-projecting vagal motoneurons and in vivo recordings of gastric tone and motility. GABAergic currents onto vagal motoneurons were decreased by OXT in stressed, but not in naïve rats. In naïve rats, microinjections of OXT in vagal brainstem nuclei-induced gastroinhibition via peripheral release of nitric oxide (NO). In stressed rats, however, the OXT-induced gastroinhibition was determined by the release of both NO and vasoactive intestinal peptide (VIP). Taken together, our data indicate that stress induces neuroplasticity in the response to OXT in the neurocircuits, which modulate gastric tone and motility. In particular, stress uncovers the OXT-mediated modulation of brainstem GABAergic currents and alters the peripheral gastric response to vagal stimulation. NEW & NOTEWORTHY The prototypical antistress hormone, oxytocin (OXT), modulates gastric tone and motility via vagal pathways, and descending hypothalamic-brainstem OXT neurocircuits play a major role in the vagally dependent adaptation of gastric motility and tone to stress. The current study suggests that in the neurocircuits, which modulate gastric tone and motility, stress induces neuroplasticity in the response to OXT and may reflect the dysregulation observed in stress-exacerbated functional motility disorders.