The potential protective effect of OT on a stress-aggravated
colitis model in rats and the involvement of OT receptors were evaluated. Holeboard test performances of Sprague-Dawley rats were videotaped for 5min to evaluate their exploratory behavior as indices of anxiety levels. A subgroup of rats was exposed to a 30-min psychological stress procedure, "water avoidance stress", for 5 consecutive days.
Colitis was induced by intracolonic administration of
2,4,6-trinitrobenzene sulfonic acid (TNBS, 30mg/ml), while the
sham group was administered with intracolonic saline. Either OT (0.5mg/kg/day; subcutaneously) or OT + OT receptor antagonist
atosiban, was given (1mg/kg/day; intraperitoneally) for 3 consecutive days after
colitis induction. On the third day, holeboard tests were performed again and the rats were decapitated. Macroscopic lesions were scored and the degree of
oxidant damage was evaluated by colonic
myeloperoxidase activity (MPO),
malondialdehyde (MDA) and
glutathione (GSH) levels, and by histological analysis.
Colitis induction inhibited exploratory behavior, indicating increased anxiety level, while exposure to stress further exaggerated the degree of anxiety. Macroscopic scores as well as MDA and MPO levels revealed that tissue damage is aggravated in the stressed group with
colitis while
antioxidant GSH levels were decreased in both
colitis and stressed
colitis groups.
Oxytocin treatment decreased the exacerbated anxiety, MPO and MDA levels and inflammatory cell infiltration and submucosal
edema while
atosiban abolished all the protective effects of OT. Thus, the results showed that the
anxiolytic and
antioxidant effects of OT are mediated via its receptors, since
atosiban reversed the protective impact of OT on colonic injury while blocking its stress-relieving effect.