title: QCM-4 a novel 5-HT3 antagonist attenuates the behavioral and biochemical alterations on chronic unpredictable mild stress model of depression in Swiss albino mice.
abstract: OBJECTIVE
  The inconsistent therapeutic outcome necessitates identifying novel compounds for the treatment of depression. Therefore, the present study is aimed at evaluating the antidepressant-like effects of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alterations in mice.
  
  
  METHODS
  Animals were subjected to different stressors for a period of 28 days. Thereafter, battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM) and open field test (OFT) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase and superoxide dismutase (SOD) were assessed in brain homogenate.
  
  
  RESULTS
  QCM-4 dose dependently reversed the CUMS induced behavioral and biochemical alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the percent time in open arm in EPM and increasing the ambulation along with the rearings and decreased number of fecal pellets in OFT. Further, biochemical alterations were attenuated by QCM-4 as indicated by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD.
  
  
  CONCLUSIONS
  QCM-4 attenuated the behavioral and biochemical derangements induced by CUMS in mice, indicating antidepressant behavior of the novel compound.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors.forename: Yeshwant
authors.initials: Y
authors.lastname: Kurhe
authors.forename: Mahesh
authors.initials: M
authors.lastname: Radhakrishnan
authors.forename: Deepali
authors.initials: D
authors.lastname: Gupta
authors.forename: Thangaraj
authors.initials: T
authors.lastname: Devadoss
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009573:Nitrites / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C000595878:3-methoxy-N-p-tolylquinoxalin-2-carboxamide; D000928:Antidepressive Agents; D009573:Nitrites; D011810:Quinoxalines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: 5-HT3 antagonist; CUMS; immobility time; lipid peroxidation; sucrose preference