PMID- 28238069
OWN - NLM
STAT- MEDLINE
DCOM- 20171201
LR  - 20190318
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 234
IP  - 7
DP  - 2017 Apr
TI  - Novel 5-HT(3) receptor antagonist QCM-4 attenuates depressive-like phenotype 
      associated with obesity in high-fat-diet-fed mice.
PG  - 1165-1179
LID - 10.1007/s00213-017-4558-0 [doi]
AB  - RATIONALE: Depression associated with obesity remains an interesting area to 
      study the biological mechanisms and novel therapeutic intervention. OBJECTIVES: 
      The present study investigates the effect of a novel 5-HT(3) receptor antagonist 
      3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on several pathogenic markers 
      of depression associated with obesity such as plasma insulin resistance, 
      hippocampal cyclic adenosine monophosphate (cAMP), brain-derived neurotrophic 
      factor (BDNF), serotonin (5-HT) concentrations, hippocampal neuronal damage, and 
      p53 protein expression in high-fat-diet (HFD)-fed mice. METHODS: Obesity was 
      experimentally induced in mice by feeding with HFD for 14 weeks followed by 
      administration of QCM-4 (1 and 2 mg/kg, p.o.)/standard escitalopram (ESC) 
      (10 mg/kg, p.o.)/vehicle (10 ml/kg, p.o.) for 28 days. Behavioral assays such as 
      sucrose preference test (SPT); forced swim test (FST); elevated plus maze (EPM); 
      biochemical assays including oral glucose tolerance tests (OGTT), insulin, cAMP, 
      BDNF, and 5-HT concentrations; and molecular assays mainly histology and 
      immunohistochemistry (IHC) of p53 protein in the dentate gyrus (DG), CA1, and CA3 
      regions of hippocampus in HFD fed mice were performed. RESULTS: Chronic treatment 
      with QCM-4 in HFD-fed mice reversed the behavioral alterations in SPT, FST, and 
      EPM. QCM-4 showed poor sensitivity for plasma glucose, improved insulin 
      sensitivity, increased hippocampal cAMP, BDNF, and 5-HT concentrations. In the 
      hippocampal DG, CA1, and CA3 regions, QCM-4 treatment improved the neuronal 
      morphology in the histopathology and inhibited p53 protein expression in IHC 
      assay in HFD-fed mice. CONCLUSION: QCM-4 attenuated the depressive-like phenotype 
      in HFD-fed mice by improving behavioral, biochemical, and molecular alterations 
      through serotonergic neuromodulation.
FAU - Kurhe, Yeshwant
AU  - Kurhe Y
AD  - Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Pilani 
      Campus, Pilani, Rajasthan, 333031, India. yashkurhe@gmail.com.
FAU - Mahesh, R
AU  - Mahesh R
AD  - Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Pilani 
      Campus, Pilani, Rajasthan, 333031, India.
FAU - Devadoss, Thangaraj
AU  - Devadoss T
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical 
      University (IMU), No. 126, Jalan Jalil Perkasa 19, 57000, Bukit Jalil, Kuala 
      Lumpur, Malaysia.
LA  - eng
PT  - Journal Article
DEP - 20170225
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (3-methoxy-N-p-tolylquinoxalin-2-carboxamide)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Quinoxalines)
RN  - 0 (Serotonin 5-HT3 Receptor Antagonists)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Animals
MH  - Anxiety/drug therapy/psychology
MH  - Brain Chemistry/drug effects
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Depression/complications/*drug therapy/psychology
MH  - Diet, High-Fat
MH  - Hippocampus/drug effects/metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Obesity/*psychology
MH  - Quinoxalines/*therapeutic use
MH  - Serotonin/metabolism
MH  - Serotonin 5-HT3 Receptor Antagonists/*therapeutic use
MH  - Swimming/psychology
MH  - Tumor Suppressor Protein p53/metabolism
OTO - NOTNLM
OT  - *BDNF
OT  - *Depression
OT  - *Obesity
OT  - *Serotonin
OT  - *p53
EDAT- 2017/02/27 06:00
MHDA- 2017/12/02 06:00
CRDT- 2017/02/27 06:00
PHST- 2016/07/20 00:00 [received]
PHST- 2017/02/02 00:00 [accepted]
PHST- 2017/02/27 06:00 [pubmed]
PHST- 2017/12/02 06:00 [medline]
PHST- 2017/02/27 06:00 [entrez]
AID - 10.1007/s00213-017-4558-0 [pii]
AID - 10.1007/s00213-017-4558-0 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2017 Apr;234(7):1165-1179. doi: 
      10.1007/s00213-017-4558-0. Epub 2017 Feb 25.