Role of AMPA receptor stimulation and TrkB signaling in the antidepressant-like effect of ketamine co-administered with a group II mGlu receptor antagonist, LY341495, in the forced swim test in rats.
Agnieszka Pałucha-Poniewiera, K. Podkowa, Andrzej Pilc
Behavioural Pharmacology September 1, 2019 DOI: 10.1097/fbp.0000000000000471 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ketamine LY341495 NBQX ANA-12 |
| Dose | 3 mg/kg ketamine, 0.1 mg/kg LY341495, 10 mg/kg NBQX |
| Duration | 40 minutes, 3 hours, and 24 hours after joint administration |
| Topics | Esketamine Ketamine |
| Key points | AMPA receptor activation is required for the antidepressant-like effect of ketamine co-administered with LY341495 at all tested time points, while TrkB receptor activation contributes to the effect only at 3 hours after administration. |
Abstract
Ketamine has been shown to induce a rapid antidepressant effect on patients with depression. In many animal models, both rapid and sustained antidepressant activities were also found in response to an antagonist of group II metabotropic glutamate receptors, LY341495, and its mechanism of action seemed to be similar in many ways to the action of ketamine. It has also been found that LY341495 enhanced the antidepressant-like activity of sub-effective doses of ketamine in rats without inducing adverse effects. Here, we investigated the role of AMPA receptor and TrkB receptor activation in the antidepressant-like effects of ketamine (3 mg/kg) co-administered with LY341495 (0.1 mg/kg), in the forced swim test in rats, at three time points (40 min, 3 h and 24 h) after joint administration of the tested compounds. It was found that the AMPA receptor antagonist NBQX (10 mg/kg) reversed the antidepressant effect of ketamine co-administered with LY341495 at all tested time points, whereas the TrkB receptor antagonist ANA-12 contributed to blockade of the effect of ketamine and LY341495 3 h after their joint administration. These results indicate that activation of AMPA receptor and BDNF-related signaling may play a role in the mechanism of antidepressant action of ketamine co-administered with LY341495.
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 13
- Role of BDNF in the pathophysiology and treatment of depression: Activity‐dependent effects distinguish rapid‐acting antidepressants European Journal of Neuroscience December 6, 2019
- ( 2R,6R )-hydroxynorketamine exerts mGlu 2 receptor-dependent antidepressant actions Proceedings of the National Academy of Sciences March 13, 2019
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Effects of esketamine and fluoxetine on depression-like behaviors in chronic variable stress: a role of plasma inflammatory factors. Frontiers in Psychiatry 2024
- Modulation of Metabotropic Glutamate Receptors as a Strategy to Improve the Efficacy and Safety of Ketamine as an Antidepressant Cells December 11, 2025
and 8 more in the library
Cites 12
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- 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
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
and 7 more in the library