State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China; Shenzhen Bay Laboratory, Shenzhen 518055, China; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: lisp@pku.edu.cn.
2 papers in the library · 15 citations · publishing 2024
In a mouse model of depression induced by corticosterone, ketamine reversed depression-like behaviors and restored disrupted synaptic signaling, including the TrkB/BDNF and eIF4E/MNK1/p-eIF2α/ubiquitin pathways. Blocking eIF4E/MNK1 signaling with eFT508 prevented ketamine's antidepressant effects, but these were restored by 7,8-DHF, a BDNF/TrkB agonist. 7,8-DHF also increased eIF4E phosphorylation and MNK1 expression and enhanced p-eIF2α levels. Ketamine appears to act through the eIF4E/BDNF signaling pathway in the hippocampus, offering new insights into its molecular mechanism.
Four compounds derived from (2R,6R;2S,6S)-hydroxynorketamine (HNK) were tested for antidepressant effects in mice. In the forced swimming test, mice given 10 mg of HNK, compound I5, or compound I6 showed significantly less immobility time at 1 hour and 7 days compared to saline controls. Compounds C and D also reduced immobility in a glass cylinder test. In the locomotor sensitization test, compounds C and D increased movement distance on days 7 and 15 relative to day 1. Both compounds induced conditioned place preference, indicating rewarding effects. The results suggest compounds C and D may have some antidepressant activity, while HNK itself produced a rapid but short-lived antidepressant effect within one week.