Ketamine improved depressive‐like behaviors via hippocampal glucocorticoid receptor in chronic stress induced‐ susceptible mice
Behavioural Brain Research May 1, 2019 Wei Wang, Le Liu, Xiu Yang et al.
Mice that showed a rise in plasma corticosterone two hours after a single social defeat stress went on to develop depressive-like behaviors after ten days of repeated defeat. Resilient mice did not show this early corticosterone increase. Susceptible mice maintained elevated corticosterone even 48 hours after the last stress. Giving corticosterone in drinking water made mice susceptible. The glucocorticoid receptor antagonist mifepristone reduced susceptibility. A single dose of ketamine improved depressive-like behaviors, lowered corticosterone, and restored glucocorticoid receptor expression and nuclear translocation in the hippocampus. Abnormal corticosterone after stress may predict susceptibility to depression, and ketamine may work by normalizing HPA axis response.