title: QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice: an approach based on behavioral and biochemical investigations.
abstract: Previous studies in our laboratory examined the antidepressant potential of 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4), a 5-HT3 receptor antagonist in acute and chronic rodent models of depression. The aim of present study was to investigate the effect of QCM-4 on chronic unpredictable mild stress (CUMS) induced depression in obese mice using behavioral based battery tests and biochemical assessments. Depressive behavior was induced in obese mice by subjecting to different stress procedures for 28 days. The results indicated that the CUMS induced severe depressive behavior in obese mice as demonstrated by a significant decreased sucrose consumption, increased immobility time in forced swim test (FST) and tail suspension test (TST), decreased percent entries and time in open arm in elevated plus maze (EPM). Moreover, CUMS significantly increased the plasma glucose, total cholesterol, triglycerides and total proteins in obese mice. Chronic treatment with QCM-4 (2 mg/kg po) and standard drug escitalopram (10 mg/kg po) significantly reversed the depressive behavioral changes (increased sucrose consumption, decreased immobility time in FST and TST, and increased the percent entries and time in open arm in EPM) and biochemical alterations (reversed the raised levels of plasma glucose, total cholesterol, triglycerides and total proteins) in obese mice subjected to CUMS. No alteration was observed in the locomotor score in obese mice. In conclusion, the results of the present study suggested that QCM-4 attenuated the depression co-morbid with obesity in mice subjected to CUMS which to some extent is mediated by reversing the "insulin resistance" or "altered plasma glucose" in obese mice.
authors: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan 333031, India. Electronic address: yashkurhe@gmail.com.
authors: Yeshwant
authors: Y
authors: Kurhe
authors: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan 333031, India.
authors: Radhakrishnan
authors: R
authors: Mahesh
authors: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan 333031, India.
authors: Deepali
authors: D
authors: Gupta
authors: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan 333031, India.
authors: Thangaraj
authors: T
authors: Devadoss
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D059305:Diet, High-Fat / Q000009:adverse effects; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: C000595878:3-methoxy-N-p-tolylquinoxalin-2-carboxamide; D000928:Antidepressive Agents; D001786:Blood Glucose; D001798:Blood Proteins; D007004:Hypoglycemic Agents; D011810:Quinoxalines; D058831:Serotonin 5-HT3 Receptor Antagonists; D014280:Triglycerides; D002784:Cholesterol
keywords: 5-HT(3) receptor antagonist; Depression; Insulin resistance; Obesity; Plasma glucose