Ketamine but not glycine potentiates antidepressant like action of citalopram in mice exposed to chronic mild stress
Veena Verma, Pankaj P. Sanone, Ashish K. Mehta, Chakra D. Tripathi
International Journal of Basic & Clinical Pharmacology August 25, 2023 DOI: 10.18203/2319-2003.ijbcp20232573 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Population | Swiss Albino male mice subjected to chronic mild stress for 6 weeks |
| Interventions | Citalopram Ketamine Glycine |
| Dose | citalopram 5 and 10 mg/kg; ketamine 17.5 and 35 mg/kg; glycine 50 and 100 mg/kg; ketamine 17.5 mg/kg + citalopram 5 mg/kg; ketamine 17.5 mg/kg + glycine 50 mg/kg |
| Duration | 6 weeks of chronic mild stress; immobility recorded for 6 min before and after drug administration |
| Measures | tail suspension test (TST), forced swim test (FST) |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine at 17.5 mg/kg combined with citalopram at 5 mg/kg significantly reduced immobility time in both the tail suspension and forced swim tests, whereas ketamine alone produced only a non-significant decrease. Glycine at 100 mg/kg significantly increased immobility in both tests. The authors suggest ketamine's potentiation of citalopram may involve NMDA receptors. |
Abstract
Background: The present study was designed to investigate the effect of citalopram, ketamine, glycine and their combinations on animal models of depression.
Methods: Swiss Albino male mice were subjected to chronic mild stress for 6 weeks for inducing depression, and randomly divided into different groups: citalopram (5 and 10 mg/kg), ketamine (17.5 and 35 mg/kg), glycine (50 and 100 mg/kg), ketamine (17.5 mg/kg) + citalopram (5 mg/kg) and ketamine (17.5 mg/kg) + glycine (50 mg/kg). Two behavioural tests were utilized for the assessment of depression, namely tail suspension test (TST) and forced swim test (FST). Immobility time was recorded for 6 min, before and after administration of drug.
Results: Citalopram (10 mg/kg) administration caused significant decrease in the immobility time in TST model only but not in FST. Citalopram (5 mg/kg) and ketamine (17.5 mg/kg) caused insignificant decrease in immobility time in both the models. Moreover, ketamine in combination with Citalopram significantly reduced the immobility time in both the models. Glycine at a dose of 100 mg/kg (but not 50 mg/kg) significantly increased the immobility time in both the models as compared to control group. Further, ketamine when administered with glycine caused increase in the immobility time on both the paradigms, though insignificant.
Conclusions: Ketamine demonstrated antidepressant like action in both TST and FST models. Moreover, it potentiated the antidepressant effect of citalopram that might be due to the role of NMDA receptors.
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
Cites 6
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity. Drug Discovery Today February 6, 2016
and 1 more in the library