The effectiveness of (R)-ketamine and its mechanism of action differ from those of (S)-ketamine in a chronic unpredictable mild stress model of depression in C57BL/6J mice.
Behavioural Brain Research October 1, 2021 A. Rafało-ulińska, A. Pałucha-poniewiera 46 citations
In a mouse model of chronic unpredictable mild stress, (R)-ketamine reduced anhedonia and apathy for up to seven days after a single dose, whereas (S)-ketamine's effects lasted only 24 hours to three days. (R)-ketamine's behavioral effects required activation of TrkB receptors, while (S)-ketamine's did not. (S)-ketamine activated mTOR and ERK pathways and increased GluA1 protein in the prefrontal cortex; (R)-ketamine increased mTOR expression without changing ERK phosphorylation. (S)-ketamine produced signs of possible side effects at the doses tested, while (R)-ketamine did not. These results suggest (R)-ketamine may be more effective, longer-lasting, and safer than (S)-ketamine.