title: 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: OBJECTIVE
  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.
  
  
  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 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. '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.
  
  
  CONCLUSIONS
  Compound '6g' exerted antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant mechanisms.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors.forename: Shvetank
authors.initials: S
authors.lastname: Bhatt
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Radhakrishnan
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Jindal
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors.forename: Thangaraj
authors.initials: T
authors.lastname: Devadoss
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors.forename: Arghya Kusum
authors.initials: AK
authors.lastname: Dhar
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology
chemical_list: C586173:(4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl)methanone; D014151:Anti-Anxiety Agents; D010879:Piperazines; D011810:Quinoxalines; D058831:Serotonin 5-HT3 Receptor Antagonists
keywords: 5-HT3 receptor antagonist; chronic unpredictable mild stress; depression; oxidative stress
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