Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade
Elena Enosyreva, Anita E. Autry, Ege Ekavalali, Lisa M Monteggia
Frontiers in Molecular Neuroscience September 11, 2015 DOI: 10.3389/fnmol.2014.00094 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Juvenile and adult (6-9 weeks old) animals |
| Interventions | Ketamine AP5 |
| Topics | Ketamine Addiction |
| Keywords | Behavior Antidepressant Development Synaptic potentiation |
| Citations | 51 |
| Key findings | Ketamine did not produce an antidepressant response or trigger synaptic potentiation in juvenile animals, indicating a developmental component to its antidepressant efficacy. |
Abstract
Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old). The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.
Comparable studies
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| Mindful attention reduces neural and self-reported cue-induced craving in smokers Treatment-seeking smokers, meditation-naïve, 12-hour abstinent | 2011 | Experimental study | n = 47 |
| DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons Rat | 2000 | Experimental study | |
| Noribogaine is a G-protein biased κ-opioid receptor agonist. | 2015 | Experimental study with binding experiments, functional assays, and computational simulations |
Citations in the library
Cited by 19
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine: NMDA Receptors and Beyond Journal of Neuroscience November 2, 2016
- Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine Current Neuropharmacology March 10, 2016
- The Antidepressant Actions of Ketamine and its Enantiomers Pharmacology & Therapeutics May 1, 2023
- Ketamine: Neuroprotective or Neurotoxic? Frontiers in Neuroscience September 10, 2021
and 14 more in the library
Cites 8
- 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
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011
and 3 more in the library