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Year : 2014  |  Volume : 46  |  Issue : 2  |  Page : 191--196

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

Shvetank Bhatt, Mahesh Radhakrishnan, Ankur Jindal, Thangaraj Devadoss, Arghya Kusum Dhar 
 Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India

Correspondence Address:
Shvetank Bhatt
Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan
India

Aim: The aim of the study was to evaluate a novel 5 HT 3 receptor antagonist (6g) on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, bodySQs 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-HT 3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) with good Log P (3.08) value and pA 2 (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. SQ6gSQ (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 SQ6gSQ (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 SQ6gSQ exerted antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant mechanisms.


How to cite this article:
Bhatt S, Radhakrishnan M, Jindal A, Devadoss T, Dhar AK. 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.Indian J Pharmacol 2014;46:191-196


How to cite this URL:
Bhatt S, Radhakrishnan M, Jindal A, Devadoss T, Dhar AK. 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. Indian J Pharmacol [serial online] 2014 [cited 2021 Sep 25 ];46:191-196
Available from: https://www.ijp-online.com/article.asp?issn=0253-7613;year=2014;volume=46;issue=2;spage=191;epage=196;aulast=Bhatt;type=0