Ketamine Rescues Hippocampal Reelin Expression and Synaptic Markers in the Repeated-Corticosterone Chronic Stress Paradigm
Jenessa N Johnston, Jonathan S. Thacker, Charissa Desjardins, Brian D. Kulyk, Raquel Romay-Tallon, Lisa E Kalynchuk, Hector J Caruncho
Frontiers in Pharmacology September 2, 2020 DOI: 10.3389/fphar.2020.559627 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study with repeated corticosterone paradigm Peer reviewed |
|---|---|
| Population | Adult male rats |
| Interventions | Ketamine Reelin |
| Topics | Ketamine Esketamine |
| Keywords | Reelin Antidepressant Synaptosomes Hippocampus |
| Citations | 25 |
| Key points | Ketamine and reelin both rescue synaptic mTOR and p-mTOR expression reduced by corticosterone, and reelin additionally restores peripheral serotonin transporter clustering. |
Abstract
Depression is the leading cause of disability worldwide, which necessitates novel therapeutics and biomarkers to approach treatment of this neuropsychiatric disorder. To assess potential mechanisms underlying the fast-acting antidepressant actions of ketamine we used a repeated corticosterone paradigm in adult male rats to assess the effects of ketamine on reelin-positive cells, a protein largely implicated in the pathophysiology of depression. We also assessed the effects of reelin and ketamine on hippocampal and cerebellar synpatosomes, and on serotonin transporter clustering in peripheral lymphocytes to determine reelin and ketamine’s impact at the synaptic and peripheral levels. Reelin and ketamine similarly rescue synaptic expression of mTOR and p-mTOR that were decreased by corticosterone. Reelin, but not ketamine, was able to rescue patterns of serotonin transporter clustering in the periphery. These findings display ketamine as a powerful modulator of reelin expression and lend strength to further evaluation of the putative fast antidepressant-like actions of reelin.
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
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications. Frontiers in Pharmacology 2024
- Time-dependent antidepressant-like effects of reelin and ketamine in the repeated-corticosterone model of chronic stress. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2024
- Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study. Translational Psychiatry November 18, 2025
- Innovative Approaches to Depression Therapy: The Antidepressant Efficacy and Mechanisms of General Anesthetics. Current Neuropharmacology April 16, 2026
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers. Journal of Anesthesia and Translational Medicine September 1, 2025
and 3 more in the library
Cites 10
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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 and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
and 5 more in the library