AMPA receptor activation-independent antidepressant actions of ketamine metabolite (S)-norketamine

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exerts robust antidepressant effects in treatment-resistant depressed patients. The precise mechanisms underlying ketamine ’s antidepressant actions remain unclear, although previous research suggests that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation plays a role. Here, we investigated whether (S)-norketamine and (R)-norketamine, the two main metabolites of (R,S)-ketamine, also pla y a significant role in ketamine’s antidepressant effects and whether the effects are mediated by AMPAR.

Source: Biological Psychiatry - May 14, 2018 Category: Psychiatry Authors: Chun Yang, Shizuka Kobayashi, Kazuhito Nakao, Chao Dong, Mei Han, Youge Qu, Qian Ren, Ji-chun Zhang, Min Ma, Hidetoh Toki, Jun-ichi Yamaguchi, Shigeyuki Chaki, Yukihiko Shirayama, Kazu Nakazawa, Toshiya Manabe, Kenji Hashimoto Tags: Archival Report Source Type: research