Introduction
Inflammatory bowel disease (IBD) represents a group of inflammatory conditions of the small intestine and colon, including Crohn’s disease (CD) and ulcerative colitis (UC). IBD is considered a primary health issue, with increasing prevalence and incidence1. However, the disease processes associated with IBD are not limited to the gastrointestinal tract. These disease processes may spread to the brain, thus increasing the risk of psychological disorders through changes to the hypothalamus-pituitary-adrenal (HPA) axis, inflammatory cytokines, and neurotransmitters2-5. For instance, depression is closely related to a clinical relapse of IBD; the occurrence of depression appears to shorten the time to clinical relapse, and increase both the onset and complications of the relapse6-8. The presence of a psychological disorder can also adversely affects the course of IBD, which can then, in turn, exacerbate psychological wellbeing9. Moreover, while psychological therapies may not have any beneficial effects on IBD activity, antidepressant and anti-anxiety drugs can reduce the effects of anti-inflammatory treatments. Further, they may even aggravate the symptoms and cause harmful side effects1011. Therefore, there is an urgent clinical need for the development of improved treatments for IBD.
Oxytocin (OT) is a neuropeptide produced by the hypothalamus and paraventricular nucleus and is released by the posterior pituitary gland12. OT plays an important role in both nonsocial and social functions, including reproduction, pain perception, immune regulation, maternal behavior, sexual behavior, pair bonding, aggression, social memory and stress13-15. Recently, OT and its receptor have been shown to have a substantial effect on several psychiatric disorders, including anxiety and autism spectrum disorder1617. The effects of OT on the brain have been previously investigated via intranasal administration of OT. Intranasal administration bypasses the blood-brain barrier allowing the delivery of OT to specific brain regions18-21. Moreover, because OT is absorbed and metabolized in the intestine and has a short half-life in blood, the oral administration of OT is problematic22. In addition, intranasal administration is convenient and noninvasive.
Interestingly, Reichmann previously reported that dextran sodium sulfate(DSS)-induced colitis impaired normal behavior in mice during a water avoidance stress test (WAST). Thus, DSS-treated mice exhibited an abnormal stress-coping ability and presented a depression-like phenotype23. The implications of intranasal OT treatment on the regulation of IBD-induced psychological disorders remains to be determined. Here, to provide insights into this phenomenon, we investigated whether intranasal OT administration can improve abnormal stress-related behavior in mice with colitis.
Materials and Methods