Short‐ and long‐term antidepressant effects of ketamine in a rat chronic unpredictable stress model
Yinghong Jiang, Yiqiang Wang, Xiaoran Sun, Bo Lian, Hongwei Sun, Gang Wang, Zhongde Du, Qi Li, Lin Sun
Brain and Behavior June 23, 2017 DOI: 10.1002/brb3.749 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Population | Adult male rats exposed to a 42-day chronic unpredictable stress (CUS) model |
| Intervention | Ketamine |
| Dose | 10 mg/kg |
| Duration | 42-day chronic unpredictable stress model; single injection on day 43 or 15 daily injections on days 43-75; behavioral assessment 24 hours (short-term) or 7 weeks (long-term) after ketamine treatment |
| Measures | Sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), water maze (WM) |
| Topics | Esketamine Ketamine |
| Citations | 63 |
| Key findings | A single 10 mg/kg ketamine injection produced rapid antidepressant-like behavioral effects in chronically stressed male rats when assessed 24 hours later, whereas 15 daily injections did not produce these effects when assessed 7 weeks after treatment; learning and memory were not significantly affected by ketamine. |
Abstract
Abstract Objective This research was aimed to evaluate the behaviors of short‐ or long‐term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS).
Background: Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory.
Methods: After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43–75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short‐term) or 7 weeks after ketamine treatment (long‐term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety‐like behavior (OF and EPM), forced swimming (FS), and water maze (WM).
Results: Short‐term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety‐eliciting situations. No significant differences in these behaviors were obtained under conditions of long‐term ketamine administration ( p > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long‐term effects of ketamine (* p < .05). Nor were significant differences obtained in learning and memory performance in rats receiving ketamine ( p > .05).
Conclusion: Taken together these findings demonstrate that a short‐term administration of ketamine induced rapid antidepressant‐like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long‐term treatment regime.
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 12
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One? Frontiers in Psychiatry May 11, 2021
- Ketamine-From an Anesthetic to a Psychiatric Drug: Mechanisms of Action, Clinical Applications and Potential Risks. Molecules June 30, 2025
- Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape bioRxiv (Cold Spring Harbor Laboratory) July 13, 2022
- Differential Actions of Ketamine on CA3-Prelimbic and CA3-Infralimbic Connection Responsivity Depend on Prior Exposure to Stress. Behavioural Brain Research June 27, 2025
and 7 more in the library
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
- 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 Journal of Neuroscience April 15, 1997
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Glutamatergic Modulators: The Future of Treating Mood Disorders? Harvard Review of Psychiatry August 1, 2010
and 12 more in the library