TY - JOUR
T1 - QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice
T2 - An approach based on behavioral and biochemical investigations
AU - Kurhe, Yeshwant
AU - Mahesh, Radhakrishnan
AU - Gupta, Deepali
AU - Devadoss, Thangaraj
N1 - Funding Information:
We are thankful to Birla Institute of Technology and Science (BITS), Pilani and University Grant Commission, India for providing support and research facilities to pursue this work.
Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2014/10/5
Y1 - 2014/10/5
N2 - 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.
AB - 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.
KW - 5-HT receptor antagonist
KW - Depression
KW - Insulin resistance
KW - Obesity
KW - Plasma glucose
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U2 - 10.1016/j.ejphar.2014.06.020
DO - 10.1016/j.ejphar.2014.06.020
M3 - Article
C2 - 24973694
AN - SCOPUS:84919430061
SN - 0014-2999
VL - 740
SP - 611
EP - 618
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -