Neuropharmacological evaluation of a novel 5-HT₃ receptor antagonist (6g) on chronic unpredictable mild stress-induced changes in behavioural and brain oxidative stress parameters in mice

Abstract

Aim:The aim of the study was to evaluate a novel 5 HT3 receptor antagonist (6g) on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body's reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to human depression, and such animal models can be used for the preclinical evaluation of antidepressants.Materials and Methods:In the present study, a novel and potential 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) with good Log P (3.08) value and pA2(7.5) values, synthesized in our laboratory was investigated to study the effects on chronic unpredictable mild stress (CUMS)-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour.Results:The results showed that CUMS caused depression-like behaviour in mice, as indicated by the significant (P < 0.05) decrease in sucrose consumption and locomotor activity and increase in immobility the forced swim test. In addition, it was found that lipid peroxidation and nitrite levels were significantly (P < 0.05) increased, whereas glutathione levels, superoxide dismutase and catalase activities decreased in brain tissue of CUMS-treated mice. ‘6g’ (1 and 2 mg/kg, p.o., 21 days) and fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly (P < 0.05) reversed the CUMS-induced behavioural (increased immobility period, reduced sucrose preference and decreased locomotor activity) and biochemical (increased lipid peroxidation; decreased glutathione levels, superoxide dismutase and catalase activities). However fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly decreased the nitrite level in the brain while ‘6g’ (1 and 2 mg/kg, p.o., 21 days) did not show significant (P < 0.05) effect on the nitrite levels in brain.Conclusion:Compound ‘6g’ exerted antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant mechanisms.

Antidepressant-Like Activity of Trans-Anethole in Unstressed Mice and Stressed Mice

“…In the present study, CUMS resulted in increase in brain lipid peroxidation and plasma nitrite levels; and decrease in reduced GSH and catalase activity. This is also supported by earlier studies [57]. Trans-anethole (25 mg/kg and 50 mg/kg, p.o) administered for 3 successive weeks significantly reversed CUMSinduced oxidative stress parameters, while only one dose (25 mg/kg) of trans-anethole significantly reversed oxidative stress parameters in unstressed mice.…”

Orientin improves depression‐like behavior and BDNF in chronic stressed mice

“…Accumulating preclinical and clinical research provide evidence that chronic stress is an important causal factor for the development of depression . Oxidative damage induced by chronic stress has been demonstrated to be involved in the etiopathogenesis of depression and anxiety . Oxidative stress damages proteins and DNA in the brain and leads to the injury and apoptosis of neurons .…”

Antidepressant-Like Activity of Flowers of Tecomella Undulata in Mice Subjected to Chronic Unpredictable Mild Stress

“…Alleviation of oxidative stress by fluoxetine has also been reported in the literature [52]. Stressful situations in rats have also been reported to significantly increase plasma nitrite levels [53,54]. The ethanol extract (100 and 200 mg/kg) and fluoxetine (20 mg/kg) per se significantly reduced nitrosative stress as indicated by reduction of the plasma nitrite levels in stressed mice as compared to vehicle-treated stressed mice.…”