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Ketamine improved depressive‐like behaviors via hippocampal glucocorticoid receptor in chronic stress induced‐ susceptible mice

Wei Wang, Le Liu, Xiu Yang, Han Gao, Qianqi Tang, L. Yin, Xiao-yu Yin, Jing-Ru Hao, D. Geng, Can Gao

Behavioural Brain Research May 1, 2019 DOI: 10.1016/j.bbr.2019.01.057 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Population Mice
Interventions Ketamine Mifepristone
Duration 10 d social defeat stress, 48 h after last defeat stress
Topics Esketamine Ketamine
Key findings Elevated plasma corticosterone after a single social defeat stress predicted later susceptibility to chronic social defeat stress, and ketamine reversed depressive-like behaviors by normalizing HPA axis function.

Abstract

HighlightsSusceptible mice showed depressive‐like behaviors upon chronic social defeat stress.Plasma corticosterone concentration might predict susceptibility to chronic stress.Abnormal glucocorticoid receptor expression was associated with susceptibility.Ketamine exerted antidepressant effect via normalizing HPA axis response. &NA; Chronic stress is an important factor for depression. Most individuals recover from stress, while some develop into depression. The pathogenesis of resilience or susceptibility remains unclear. Stress activates the hypothalamic‐pituitary‐adrenal (HPA) axis and releases stress hormones to regulate individual response to stress. Hence, we assessed the effects of chronic social defeat stress (CSDS) on susceptible behaviors, plasma corticosterone (CORT) concentration, glucocorticoid receptor (GR) expressions in hippocampus and medial prefrontal cortex (mPFC). Mice that plasma CORT concentration is increased 2 h after single social defeat stress developed into susceptible mice after 10 d social defeat stress. The plasma CORT concentration was still higher than that of resilient mice 48 h after the last defeat stress. Mice administered CORT via drinking water showed susceptibility. Mifepristone, a GR antagonist improved susceptibility to chronic stress. Single dose ketamine treatment improved depressive‐like behaviors, decreased plasma CORT concentration, rescued GR expression and nuclear translocation in the hippocampus of susceptible mice. These results suggested that abnormal CORT concentration after stress may predict susceptibility to depression in clinic. Ketamine may exert the antidepressant effect via normalizing HPA axis response and have significance in the clinic.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study Year Design Participants
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats 2010 Observational study
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats 1997 Dose-response study with microdialysis and behavioral testing
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice 2016 Preclinical study
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats 1983 Experimental study
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice 2015 Experimental study

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Esketamine Ketamine Depression