Episodic-like memory impairment induced by sub-anaesthetic doses of ketamine.
Ingrid Brasilino Montenegro Bento De Souza, Ywlliane da Silva Rodrigues Meurer, Priscila Macedo Tavares, Karen Cristina Pugliane, Ramón Hypolito Lima, Regina Helena Silva, Flávio Freitas Barbosa
Behavioural Brain Research February 1, 2019 DOI: 10.1016/j.bbr.2018.10.031 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Intervention | Ketamine |
| Dose | 8 mg/kg or 15 mg/kg (i.p.) |
| Measures | WWWhen/ELM task, c-Fos expression |
| Topics | Ketamine Esketamine |
| Keywords | Episodic-like memory Wistar rats C-fos |
| Key findings | Ketamine at 8 mg/kg or 15 mg/kg given after the second sample impaired formation of episodic-like memory across all three elements (what, where, when), whereas untreated and saline-treated rats integrated them. The 15 mg/kg dose also increased c-Fos expression in the dorsal CA1 subregion relative to saline. The authors interpret this as NMDA receptor antagonism concurrently impairing episodic-like memory formation and increasing neuronal activation in dorsal CA1. |
Abstract
Episodic-like memory refers to integration of where and when a certain event (what) happened. The glutamatergic neurotransmission, particularly AMPA and NMDA receptors, in the dorsal hippocampus mediates episodic recall. Ketamine is a non-competitive NMDA antagonist with effect on cognitive performance and plasticity. The goal of this study was to evaluate the acute action of ketamine on behavioural and neurochemical aspects of episodic-like memory (WWWhen/ELM task) through immediate-early gene expression (IEG), c-Fos, in the dorsal hippocampus. Animals received saline 0.9% or ketamine at 8 mg/kg or 15 mg/kg (i.p.) immediately after the second sample. Our data indicate that untreated and saline rats integrate the three elements of episodic-like memory. Conversely, animals treated with ketamine showed impairment of ELM formation. In addition, the highest dose of ketamine increased c-Fos expression in dorsal CA1 subregion when compared to saline rats. Our results indicate that the antagonism of NMDA concurrently impair ELM formation of all three aspects of ELM and increase neuronal activation in dorsal CA1.
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 3
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- Ketamine differentially affects implicit and explicit memory processes in rats. Psychopharmacology June 1, 2025
- Acute ketamine withdrawal disrupts memory and monoaminergic neurotransmission in adolescent female rats. Behavioural Brain Research March 28, 2026
Cites 10
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Salvinorin A fails to substitute for the discriminative stimulus effects of LSD or ketamine in Sprague-Dawley rats. Pharmacology, Biochemistry, and Behavior September 1, 2010
- Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice Neuroreport September 28, 2016
- Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology January 2012
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