4.5 Article

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

期刊

EUROPEAN PSYCHIATRY
卷 29, 期 7, 页码 419-423

出版社

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.eurpsy.2013.10.005

关键词

Ketamine; Depression; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; Mammalian target of rapamycin; Brain-derived neurotrophic factor

资金

  1. National Natural Science Foundation of China [30872424, 81271216]

向作者/读者索取更多资源

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 alpha-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. (C) 2013 Elsevier Masson SAS. All rights reserved.

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