Subanesthetic ketamine exerts antidepressant-like effects in adult rats exposed to juvenile stress.
Katsuhiro Aikawa, Takayuki Yoshida, Yu Ohmura, K. Lyttle, M. Yoshioka, Y. Morimoto
Brain Research June 13, 2020 DOI: 10.1016/j.brainres.2020.146980 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Adult rats that had been subjected to juvenile stress |
| Intervention | Ketamine |
| Dose | 10 mg/kg |
| Topics | Esketamine Ketamine |
| Key points | Ketamine (10 mg/kg) attenuated depressive-like behavior and reversed electrophysiological and morphological alterations in the prelimbic cortex caused by juvenile stress in rats. |
Abstract
Juvenile stress, like that caused by childhood maltreatment, is a significant risk factor for psychiatric disorders such as depression later in life. Recently, the antidepressant effect of ketamine, a noncompetitive N-methyl-d-aspartate receptor antagonist, has been widely investigated. However, little is known regarding its efficacy against depressive-like alterations caused by juvenile stress, which is clinically relevant in human depression. In the present study, we evaluated the antidepressant-like effect of ketamine in adult rats that had been subjected to juvenile stress. Depressive-like behavior was assessed using the forced swim test (FST), and electrophysiological and morphological alterations in the layer V pyramidal cells of the prelimbic cortex were examined using whole-cell patch-clamp recordings and subsequent recording-cell specific fluorescence imaging. We demonstrated that ketamine (10 mg/kg) attenuated the increased immobility time caused by juvenile stress in the FST, restored the diminished excitatory postsynaptic currents, and caused atrophic changes in the apical dendritic spines. Ketamine's effects reversing impaired excitatory/inhibitory ratio of postsynaptic currents were also revealed. These results indicated that ketamine could be effective in reversing the depression-like alterations caused by juvenile stress.
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 |
Citations in the library
Cited by 3
- Low-dose S-ketamine exerts antidepressant-like effects via enhanced hippocampal synaptic plasticity in postpartum depression rats. Neurobiology of Stress 2022
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD. Psychopharmacology June 1, 2025
- Shared effects of electroconvulsive shocks and ketamine on neuroplasticity: A systematic review of animal models of depression. Neuroscience & Biobehavioral Reviews September 1, 2024
Cites 17
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
and 12 more in the library