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Behav Brain Res. 2017 Sep 29;335:63-70. doi: 10.1016/j.bbr.2017.08.011. Epub 2017 Aug 8.

Venlafaxine exerts antidepressant effects possibly by activating MAPK-ERK1/2 and P13K-AKT pathways in the hippocampus.

Author information

1
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
2
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
3
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China.
4
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.
5
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
6
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
7
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China. Electronic address: xiepeng@cqmu.edu.cn.

Abstract

Serotonin noradrenaline reuptake inhibitors are effective antidepressant drugs, which include venlafaxine and duloxetine. Venlafaxine is commonly used in a clinical context, but the molecular biological mechanisms behind its effects have not been fully determined. Here, we explored the potential biological effects of venlafaxine on mouse hippocampus. Mice were randomly divided into two groups and injected daily with 0.9% NaCl solution or venlafaxine. A GC-MS-based metabolomic approach was used to identify possible metabolic differences between these groups, and the key proteins involved in the relevant pathways were validated by western blotting. In our experiments, 27 hippocampal metabolites that distinguished the venlafaxine group from the control group were identified. These differential metabolites were subjected to Ingenuity Pathway Analysis, which revealed that they were strongly related to two metabolic pathways (MAPK-ERK1/2 and P13K-AKT signaling pathways). Six key proteins, BDNF, p-c-Raf, p-MAPK, p-MEK, p-AKT, and CREB, were verified by western blotting and the results were consistent with the differential metabolites identified by GC-MS. This study sheds light on the biological mechanisms underlying the effects of venlafaxine.

KEYWORDS:

Antidepressant; Hippocampus; Mechanism; Metabolomics; Venlafaxine; Western blotting

PMID:
28797602
DOI:
10.1016/j.bbr.2017.08.011
[Indexed for MEDLINE]

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