CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy.
Anita J Bechtholt-Gompf, Karen L Smith, Catherine S John, Hannah H Kang, William A Carlezon, Bruce M Cohen, Dost Öngür
Psychopharmacology June 2011 DOI: 10.1007/s00213-011-2169-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | CD-1 and Balb/cJ mice |
| Interventions | Ketamine MK-801 Desipramine |
| Duration | 1-week follow-up |
| Measures | Tail suspension test (TST), Forced swimming test (FST) |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine and MK-801 did not produce lasting antidepressant-like effects in mice one week after administration, despite short-term effects in some tests. The authors argue that TST and FST are not sensitive to long-lasting effects and do not model ketamine's therapeutic effects in humans. |
Abstract
In patients, ketamine is a fast-acting antidepressant that can induce long-lasting symptom relief. Similar rapid effects have been reported in rodents, but reports of lasting effects are limited. We sought to extend past findings by examining dose-response curves that overlap with the individual doses previously reported to induce lasting effects in rodents and determining whether effects generalize to the tail suspension test (TST) and Balb/cJ mice. Using common tests of antidepressant efficacy we first confirmed our ability to detect the effects of desipramine, a well-characterized antidepressant drug. Next, we sought to determine whether two non-competitive NMDA antagonists, ketamine and MK-801, had long-lasting antidepressant-like effects in CD-1 mice, a strain that has often been used to demonstrate the short-term antidepressant-like effects of ketamine. Finally, we examined the short- and long-term effects of ketamine in a mouse strain that is more sensitive to antidepressant-like effects, Balb/cJ mice. In CD-1 mice, desipramine treatment yielded significant short-term antidepressant-like effects in the TST and the forced swimming test (FST). However, no significant enduring effects of ketamine or MK-801 were observed 1 week later. Short-term effects of ketamine in the TST were observed in Balb/cJ mice, but lasting effects were absent 1 week later. Although the TST and FST have been widely used to detect antidepressant-like effects in mice, they do not appear to be sensitive to long-lasting antidepressant-like effects of ketamine in mice and, therefore, do not model the therapeutic effects of ketamine that have been reported in humans with major depression.
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 14
- Antidepressant mechanism of ketamine: perspective from preclinical studies Frontiers in Neuroscience July 21, 2015
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- 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
- Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents Neurotoxicity Research June 2, 2017
- Partial mGlu5 receptor NAM, M-5MPEP, induces rapid and sustained antidepressant-like effects in the BDNF-dependent mechanism and enhances (R)-ketamine action in mice. Pharmacological Reports June 1, 2024
and 9 more in the library
Cites 16
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial The International Journal of Neuropsychopharmacology March 17, 2009
- Brain-Derived Neurotrophic Factor and Initial Antidepressant Response to anN-Methyl-D-Aspartate Antagonist The Journal of Clinical Psychiatry September 8, 2009
- Intravenous ketamine therapy in a patient with a treatment-resistant major depression Swiss Medical Weekly April 21, 2007
- Oral Administration of the NMDA Receptor Antagonist S-Ketamine as Add-On Therapy of Depression: A Case Series Pharmacopsychiatry December 11, 2009
and 11 more in the library