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 5 min 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, 30 mg/ml), while the sham group was administered with intracolonic saline. Either OT (0.5 mg/kg/day; subcutaneously) OF OT + OT receptor antagonist atosiban, was given (I mg/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. (C) 2009 Elsevier B.V. All rights reserved.