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Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex

Published online by Cambridge University Press:  15 April 2020

W. Zhou ,
N. Wang ,
C. Yang ,
X.-M. Li ,
Z.-Q. Zhou  and
J.-J. Yang
W. Zhou
Affiliation:
Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing210002, China
N. Wang
Affiliation:
Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing210002, China
C. Yang
Affiliation:
Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing210002, China
X.-M. Li
Affiliation:
Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing210002, China
Z.-Q. Zhou*
Affiliation:
Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing210002, China
J.-J. Yang*
Affiliation:
Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing210002, China
*
**Co-corresponding author. E-mail addresses: zq_zhou@163.com (Z.-Q. Zhou), yjyangjj@126.com (J.-J. Yang).
*Corresponding author. Tel.: +86 25 52323834; fax: +86 25 84806839.
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Abstract

Ketamine exerts fast acting, robust, and lasting antidepressant effects in a sub-anesthetic dose, however, the underlying mechanisms are still not fully elucidated. Recent studies have suggested that ketamine's antidepressant effects are probably attributed to the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The present study aimed to observe the effects of AMPA receptor modulators on mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF) expression during the procedure of ketamine exerting antidepressant effects. Therefore, we pretreated rats with NBQX, an AMPA receptor antagonist, or CX546, an AMPA receptor agonist, and subsequently observed the immobility time during the forced swimming test (FST) and the hippocampal and prefrontal cortical levels of mTOR and BDNF. The results showed ketamine decreased the immobility time of rats during the FST and increased the hippocampal and prefrontal cortical mTOR and BDNF. NBQX pretreatment significantly increased the immobility time and decreased the levels of mTOR and BDNF when compared with vehicle 1 (DMSO) pretreatment. CX546 pretreatment significantly decreased the immobility time and increased the levels of mTOR and BDNF when compared with vehicle 2 (DMSO + ethanol) pretreatment. Our results suggest ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex.

Keywords

KetamineDepressionα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidMammalian target of rapamycinBrain-derived neurotrophic factor
Type
Original article
Information
European Psychiatry , Volume 29 , Issue 7 , September 2014 , pp. 419 - 423
Copyright
Copyright © 2013 Elsevier Masson SAS

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Footnotes

1

The two authors contributed equally to this work.

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