Correction of depressive-like state in rats induced by social stress using a new 3-substituted thietane-1,1-dioxide derivative

Introduction. Among the various animal models of depression used to study the pathogenesis of depression and to evaluate the antidepressant action of new compounds, models based on social stress are characterized by high constructive, face and predictive validity. The rat model of depression based on the repeated social defeats allows to induce a depressive-like state corresponding to depression in humans and to evaluate the effect of new substances with antidepressant activity. Aim. To study the antidepressant effect of 3-ethoxythietane-1,1-dioxide (3ETD) on rats using resident-intruder paradigm. Materials and methods. White outbred male rats weighing 200–250 g (intruders) received 3ETD (2 mg/kg, groups "3ETD" and "Stress + 3ETD") or saline (groups "Control" and "Stress") intraperitoneally daily for 24 days. Thirty minutes after the administration, the animals of the "Stress" and "Stress + 3ETD" groups were subjected to 10-minute interaction with the residents (outbred male rats weighing 350–400 g). On day +23, intruders were tested in the forced swimming test, on day +24, the open field and elevated plus maze tests were performed. The body weight of the intruders and the amount of food consumed were recorded daily. At the end of the experiment, the weight coefficients of their internal organs were recorded. Results and discussion. Chronic repeated confrontation with residents led to the development of a depressive-like state in intruders by day +23. 3ETD exhibited antidepressant properties, eliminating the effects of social stress in intruders: 3ETD reduced despair behavior in the forced swimming test, increased exploratory, social, and motor activity of animals, the proportion of active forms of protective behavior, and reduced the proportion of passive forms during the resident-intruder interaction. Conclusion. 3ETD, when administered intraperitoneally daily at a dose of 2 mg/kg for 24 days, exhibited a pronounced antidepressant effect, eliminating the depressive-like state in rats caused by repeated social defeats.