PMID- 24634580
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140317
LR  - 20211021
IS  - 1177-3928 (Print)
IS  - 1177-3928 (Electronic)
IS  - 1177-3928 (Linking)
VI  - 8
DP  - 2014
TI  - The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB 
      and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress 
      (UCMS)-Exposed Mice.
PG  - 11-21
LID - 10.4137/DTI.S13870 [doi]
AB  - Agomelatine, a novel antidepressant with established clinical efficacy, acts as 
      an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C 
      receptors. The present study was undertaken to investigate whether chronic 
      treatment with agomelatine would block unpredictable chronic mild stress 
      (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), 
      modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris 
      water maze (MWM) tests. Moreover, the effects of stress and agomelatine on 
      brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate 
      (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) 
      levels in the hippocampus was also determined using quantitative real-time 
      polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with 
      agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five 
      weeks. The results of this study revealed that UCMS-exposed animals exhibited 
      memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic 
      administration of melatonin had a positive effect in the PA and +mEPM tests, 
      whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked 
      stress-induced impairment in visual memory in the NOR test and reversed spatial 
      learning and memory impairment in the stressed group in the MWM test. 
      Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were 
      downregulated in UCMS-exposed mice, and these alterations were reversed by 
      chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important 
      role in blocking stress-induced hippocampal memory deterioration and activates 
      molecular mechanisms of memory storage in response to a learning experience.
FAU - Gumuslu, Esen
AU  - Gumuslu E
AD  - Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, 
      Turkey.
FAU - Mutlu, Oguz
AU  - Mutlu O
AD  - Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
FAU - Sunnetci, Deniz
AU  - Sunnetci D
AD  - Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, 
      Turkey.
FAU - Ulak, Guner
AU  - Ulak G
AD  - Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
FAU - Celikyurt, Ipek K
AU  - Celikyurt IK
AD  - Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
FAU - Cine, Naci
AU  - Cine N
AD  - Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, 
      Turkey.
FAU - Akar, Furuzan
AU  - Akar F
AD  - Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
FAU - Savli, Hakan
AU  - Savli H
AD  - Department of Medical Genetics, Kocaeli University Medical Faculty, Kocaeli, 
      Turkey.
FAU - Erden, Faruk
AU  - Erden F
AD  - Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
LA  - eng
PT  - Journal Article
DEP - 20140305
PL  - Italy
TA  - Drug Target Insights
JT  - Drug target insights
JID - 101310097
PMC - PMC3948735
OTO - NOTNLM
OT  - BDNF
OT  - CREB
OT  - agomelatine
OT  - depression
OT  - melatonin
OT  - memory
EDAT- 2014/03/19 06:00
MHDA- 2014/03/19 06:01
PMCR- 2014/03/05
CRDT- 2014/03/18 06:00
PHST- 2013/12/11 00:00 [received]
PHST- 2014/01/19 00:00 [revised]
PHST- 2014/02/06 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/03/19 06:01 [medline]
PHST- 2014/03/05 00:00 [pmc-release]
AID - dti-8-2014-011 [pii]
AID - 10.4137/DTI.S13870 [doi]
PST - epublish
SO  - Drug Target Insights. 2014 Mar 5;8:11-21. doi: 10.4137/DTI.S13870. eCollection 
      2014.