title: Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex.
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.
authors: Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing 210002, China.
authors: W
authors: W
authors: Zhou
authors: Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing 210002, China.
authors: N
authors: N
authors: Wang
authors: Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing 210002, China.
authors: C
authors: C
authors: Yang
authors: Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing 210002, China.
authors: X-M
authors: XM
authors: Li
authors: Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing 210002, China. Electronic address: zq_zhou@163.com.
authors: Z-Q
authors: ZQ
authors: Zhou
authors: Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305, East Zhongshan Road, Nanjing 210002, China. Electronic address: yjyangjj@126.com.
authors: J-J
authors: JJ
authors: Yang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C443080:1-(1,4-benzodioxan-6-ylcarbonyl)piperidine; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D004149:Dioxoles; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D007649:Ketamine; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: Brain-derived neurotrophic factor; Depression; Ketamine; Mammalian target of rapamycin; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid