PMID- 29379991
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 391
IP  - 4
DP  - 2018 Apr
TI  - Metformin potentiates cognitive and antidepressant effects of fluoxetine in rats 
      exposed to chronic restraint stress and high fat diet: potential involvement of 
      hippocampal c-Jun repression.
PG  - 407-422
LID - 10.1007/s00210-018-1466-8 [doi]
AB  - Several hypotheses link high fat diet (HFD) with the pathophysiology of 
      depression and its response to antidepressants. This study aimed to determine the 
      effect of metformin (MET) on the cognitive and antidepressant activity of 
      fluoxetine (FLU) through its effect on c-Jun expression. Behavioral, cognitive 
      function, biochemical, and histopathological studies were performed in non-HFD- 
      and HFD-fed rats exposed to chronic restraint stress (CRS). Stressed group showed 
      cognitive impairment, depressive-like symptoms, disturbed glucose homeostasis and 
      lipid profile, reduced adiponectin level, brain-derived neurotrophic factor 
      (BDNF) expression, and increased corticosterone and c-Jun. All these were 
      aggravated by HFD. MET, FLU and their combination produced significant 
      improvement in lipid profile with significant increase in adiponectin and BDNF 
      expression. Corticosterone, body weight and insulin resistance showed significant 
      decrease in the treated groups. Moreover, there was a significant decrease in 
      hippocampal c Jun expression. There was a significant preferable effect toward 
      the combination. Conclusion, MET may decrease the refractoriness to FLU and 
      improves the cognition in individuals who are fed on HFD.
FAU - Khedr, Sara A
AU  - Khedr SA
AD  - Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, 
      Egypt.
FAU - Elmelgy, Ahmed A
AU  - Elmelgy AA
AD  - Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, 
      Egypt.
FAU - El-Kharashi, Omnyah A
AU  - El-Kharashi OA
AUID- ORCID: 0000-0003-2825-2907
AD  - Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, 
      Egypt. omnyah2011@gmail.com.
FAU - Abd-Alkhalek, Hadwa A
AU  - Abd-Alkhalek HA
AD  - Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams 
      University, Cairo, Egypt.
FAU - Louka, Manal L
AU  - Louka ML
AD  - Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, 
      Ain Shams University, Cairo, Egypt.
FAU - Sallam, Hoda A
AU  - Sallam HA
AD  - Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, 
      Egypt.
FAU - Aboul-Fotouh, Sawsan
AU  - Aboul-Fotouh S
AD  - Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, 
      Egypt.
LA  - eng
PT  - Journal Article
DEP - 20180129
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Antidepressive Agents)
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Cognition/drug effects
MH  - Diet, High-Fat
MH  - Drug Synergism
MH  - Fluoxetine/*pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Hypoglycemic Agents/*pharmacology
MH  - Male
MH  - Metformin/*pharmacology
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - Rats, Wistar
MH  - Restraint, Physical
MH  - Stress, Psychological/*metabolism/*psychology
OTO - NOTNLM
OT  - Depression
OT  - Fluoxetine
OT  - HFD
OT  - Metformin
OT  - Rat
OT  - c-Jun
EDAT- 2018/01/31 06:00
MHDA- 2018/11/27 06:00
CRDT- 2018/01/31 06:00
PHST- 2017/09/30 00:00 [received]
PHST- 2018/01/09 00:00 [accepted]
PHST- 2018/01/31 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/01/31 06:00 [entrez]
AID - 10.1007/s00210-018-1466-8 [pii]
AID - 10.1007/s00210-018-1466-8 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2018 Apr;391(4):407-422. doi: 
      10.1007/s00210-018-1466-8. Epub 2018 Jan 29.