Ketamine differentially affects implicit and explicit memory processes in rats.
Bahar Yuksel, Zeynep Sen, Gunes Unal
Psychopharmacology June 1, 2025 DOI: 10.1007/s00213-024-06720-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult Wistar rats |
| Intervention | Ketamine |
| Dose | 10 mg/kg, IP |
| Topics | Ketamine Esketamine |
| Keywords | Explicit memory Fear conditioning Implicit memory Morris water maze Memory research Behavioral neuroscience Animal studies Fear learning |
| Citations | 2 |
| Key findings | Ketamine at an antidepressant dose partially impairs fear extinction but facilitates reversal spatial learning, without affecting encoding or retrieval of cued fear or spatial memory. |
Abstract
Ketamine, a non-competitive NMDA receptor antagonist, produces antidepressant effects at subanesthetic doses. The therapeutic effect, however, is often accompanied by cognitive side effects, including memory impairments. Yet, the specific effects of ketamine on different processes of implicit and explicit memory remain to be elucidated. We examined the effect of an antidepressant dose of ketamine (10 mg/kg, IP) on the encoding, retrieval, and modulation processes of fear memory and spatial memory in adult Wistar rats. Ketamine was administered before the fear acquisition, retrieval, or extinction procedures in a Pavlovian fear conditioning task. In another set of experiments, it was administered before the training, probe trial, or reversal training phases of the Morris Water Maze (MWM). The antidepressant dose of ketamine partially impaired fear extinction when administered before the acquisition or retrieval. In contrast, it facilitated memory modulation and decreased the escape latency in the first day of reversal training in the MWM when administered before the training or reversal training sessions. Encoding or retrieval performance in either type of memory was not affected. These findings show that ketamine does not impair the acquisition or retrieval processes of cued fear or spatial memory; but exerts differential effects on memory modulation of these implicit and explicit memory paradigms, by disrupting fear extinction and facilitating reversal spatial learning.
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
Cites 16
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? The Journal of Clinical Psychiatry July 20, 2017
- Ketamine Effects on Memory Reconsolidation Favor a Learning Model of Delusions PLoS One June 12, 2013
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
and 11 more in the library