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