title: Neuropharmacological effect of novel 5-HT3 receptor antagonist, N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) on chronic unpredictable mild stress-induced molecular and cellular response: Behavioural and biochemical evidences.
abstract: BACKGROUND
  Chronic unpredictable stressors can produce a situation similar to human depression and such animal models can be used for the preclinical evaluation of antidepressants. The 5-HT3 receptor antagonists modulate serotonergic pathways and show antidepressant-like effect in various animal models of depression.
  
  
  METHODS
  In this study, a novel and potential 5-HT3 receptor antagonist N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) with good Log P (2.52) value and pA2 (7.6) values, synthesized in our laboratory was explore to study the effects on 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
  CUMS caused depression-like behaviour in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test (FST) while there was no significant effect on spontaneous locomotor activity (SLA) observed. In addition it was found that lipid peroxide and nitrite levels were significantly increased, whereas glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were decreased in brain tissue of CUMS-treated mice. Compound 6n (1 and 2mg/kg, po, 21 days) and fluoxetine treatment (20mg/kg, po, 21 days) significantly altered the CUMS-induced behavioural (increased immobility period, reduced sucrose preference) and biochemical (increased lipid peroxidation, increased brain nitrite; decreased GSH, SOD and CAT levels) parameters while there was no significant effect of observed on SLA.
  
  
  CONCLUSIONS
  Compound 6n produced antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant enzyme activity up to significant level.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India. Electronic address: shvetankbhatt@gmail.com.
authors.forename: Shvetank
authors.initials: S
authors.lastname: Bhatt
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahesh
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Jindal
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India.
authors.forename: Thangaraj
authors.initials: T
authors.lastname: Devadoss
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; C000597539:N-n-propyl-3-ethoxyquinoxaline-2-carboxamide; D011810:Quinoxalines; D058831:Serotonin 5-HT3 Receptor Antagonists; D005473:Fluoxetine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: 5-HT(3) receptor antagonist; 6n; CUMS; Catalase; Glutathione