Regulation of stress‐induced gastric ulcers via central oxytocin and a potential mechanism through the VTA‐NAc dopamine pathway

Abstract

Background Oxytocin (OT) plays an important role in regulating gastric function. How OT regulates stress‐induced gastric ulcers is not understood. We investigated OT's protective role in stress‐induced gastric ulcers, with a focus on OT's interaction with the ventral tegmental area (VTA) to nucleus accumbens (NAc) dopamine pathway. Methods Drugs administration into the rats brain nuclei by brain stereotaxic apparatus, to examine related changes in gastric ulcer index, pH of gastric content, and mucus secretion, and to determine complex interactions between OT and DA systems in the regulation of stress and gastric functions. Key Results Neurons in the VTA were co‐immunoreactive for the OT receptor (OTR) and DA. In a rat model of stress‐induced ulcer, water‐immersion restricted stress, direct administration of OT into the VTA significantly reduced gastric ulcer index and increased the pH of gastric content and mucus secretion. OT's effects were eliminated by pretreatment with the OTR antagonist atosiban in the VTA and weakened with pretreatment of the DA D2 receptor (DA D2R) antagonist raclopride in the NAc. In OTR gene knockout (Oxtr−/−) mice, OT's protective effect was lost. OT administered to the VTA of dorsal motor nucleus of the vagus (DMV)‐lesioned rats had minimal protective effects on gastric mucosa. Conclusions and Inferences This study provides important data necessary for a deeper understanding of the complex interactions between OT and DA systems in the regulation of stress and gastric functions. It provides relevant mechanistic clues into OT's role as a protective factor against stress‐induced changes to gastric function.

Resilience to stress and social touch

“…This brain circuit plays an important role in the motivation to carry out a social behavior and serves as a natural reinforcer in some mammals [ 40 ] ( Figure 1 ). There is a high density of oxytocin receptors expressed in the VTA-NAc-DA circuit which stimulates its functioning during stress [ 41 , 42 ] ( Figure 1 ).…”

Electroacupuncture ameliorates peptic ulcer disease in association with gastroduodenal microbiota modulation in mice

“…In addition, the role of DA, TFF, and VIP in the occurrence and development of PUD cannot be ignored. Some studies have shown that regulating DA can ameliorate gastric ulcer (Leng et al, 2019). TFF is a small molecular polypeptide secreted by gastrointestinal mucus cells.…”

Gastroprotective Mechanisms

“…Gastric neurons act on gastric motility, interact with hormones, regulate HCl and bicarbonate secretion, and induce immune responses [74,76,78,79]. As an example of the interaction with hormones, oxytocin (OT) administered in the ventral tegmental area (VTA) can activate dopamine neurons in the dopamine pathway in the nucleus accumbens through OT receptors and improve the dysfunction caused by stress in the gastric mucosa, reducing the ulcer area, stimulating mucus production, and increasing gastric pH [80].…”