Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system.
Fatemeh Khakpai, Mohaddeseh Ebrahimi-Ghiri, Sakineh Alijanpour, M. Zarrindast
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 1, 2019 DOI: 10.1016/j.biopha.2019.108717 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine ACPA AM251 GP1a AM630 |
| Dose | 5 and 10 mg/kg ketamine; 1 mg/kg ACPA; 1 mg/kg AM251; 2 mg/kg GP1a; 0.5 mg/kg AM630 |
| Topics | Esketamine Ketamine |
| Key findings | Combining ineffective doses of ketamine with cannabinoid receptor antagonists produced antidepressant-like effects in mice. |
Abstract
The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses using the forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) in mice. Our results revealed that intra-peritoneal (i.p.) injection of ketamine (5 and 10 mg/kg), a non-competitive NMDA antagonist, dose-dependently produced antidepressant-like effect in the FST. Moreover, i.p. administration of both CB1 and CB2 receptor drugs: ACPA (1 mg/kg; CB1 receptor agonist), AM251 (1 mg/kg; CB1 receptor antagonist), GP1a (2 mg/kg; CB2 receptor agonist) and AM630 (0.5 mg/kg; CB2 receptor antagonist) exhibited antidepressant action. Interestingly, the concomitant administration of ineffective doses of ketamine and cannabinoid receptor antagonists provoked the antidepressant-like effects as compared to control group. It should be considered, all above mentioned doses of drugs could not change locomotor activity in the OFT. It seems that possible interaction between ketamine and cannabinoid system may modulate depression-related behavior.
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 8
- The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage. International Journal of Molecular Sciences April 10, 2025
- The CB2-PKC pathway is involved in esketamine-induced anti-inflammation in BV-2 microglial cells exposed to lipopolysaccharides. American Journal of Translational Research 2024
- Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions Psychiatry Research August 18, 2025
- Monoamine neurotransmitter-related gene-based genome-wide association study of low-dose ketamine in patients with treatment-resistant depression. Journal of Psychopharmacology March 24, 2025
- Evaluation of Histopathologic Findings and Safety of Intravitreal Ketamine Administration on Vitreoretinal Tissue in Rat Model: A Pilot Study. Journal of current ophthalmology 2023
and 3 more in the library
Cites 11
- 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
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Addictive potential of novel treatments for refractory depression and anxiety Neuropsychiatric Disease and Treatment June 1, 2018
- The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation? Pharmacology & Therapeutics October 2018
and 6 more in the library