Correction of Rat Behavior Under Conditions of Zoosocial Stress Using a New Thietane-Containing Heterocyclic Compound: An Exploratory Experimental Study

BACKGROUND: Zoosocial interaction (ZSI), which possesses high predictive validity, phenomenological similarity to human depression, and similar pathophysiological mechanisms, allows for detailed characterization of the antidepressant effect of new compounds.

AIM: To study the effect of 5-bromo-2-(thietan-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (compound 5BTDT) on rat behavior in the ZSI model.

METHODS: The ZSI model was reproduced in outbred white rats (n = 24), divided into four groups: vehicle, compound 5BTDT, stress, and stress + compound 5BTDT. The model was established through daily intermale confrontations between intruders and residents (from day 0 to day +5). Compound 5BTDT was administered intraperitoneally for 7 days at 8.5 mg/kg/day. The effect of the compound on intruder behavior was assessed during a 10-minute interaction with residents (from day 0 to day +5), as well as in the forced swimming test (day +5), open field test, and elevated plus maze (day +6). Additionally, body weight, food consumption (from day –1 to day +6), and internal organ weights (at autopsy, day +6) were recorded. Statistical analysis was performed using R software version 3.5.1 (R Foundation for Statistical Computing, Austria). Effect size was estimated as a percentage relative to the reference group or baseline. The Wilcoxon test (for dependent and independent samples) was used for comparisons; results are presented as V or W statistics and p-values.

RESULTS: Compound 5BTDT exhibited antidepressant activity, significantly reducing the duration of immobilization in the forced swimming test in intact rats (by 55.2% ; W = 31; p = 0.045). In stressed animals, a decrease in this parameter by 46.4% was observed (W = 24; p = 0.336). The compound also counteracted ZSI-induced behavioral changes in intruders, increasing active control over the social environment: it increased the proportion of defensive behavior (by 7.3% ; V = 1; p = 0.045) and social interaction (by 0.8%; due to an increase in fighting by 0.5%; V = 6; p = 0.065), and also reduced the intensity of social investigation (by 6.1%; V = 1; p = 0.066). Behavior in the elevated plus maze and open field tests, as well as body weight gain in stressed and intact rats following administration of compound 5BTDT, did not change. The compound prevented ZSI-induced thymus atrophy.

CONCLUSION: Under conditions of intermale confrontations, compound 5BTDT exerts an antidepressant effect and contributes to the correction of intruder behavioral responses to stress exposure.