Impaired Spatial Memory after Ketamine Administration in Chronic Low Doses
Carlos Venâncio, Ana Magalhães, Luís Antunes, Teresa Summavielle
Current Neuropharmacology March 1, 2011 DOI: 10.2174/157015911795016912 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adult Wistar rats |
| Intervention | Ketamine |
| Dose | 5 and 10 mg/kg twice daily |
| Duration | 14 days of administration, testing one week later |
| Topics | Esketamine Ketamine |
| Key findings | Rats chronically exposed to 5 mg/kg ketamine twice daily for 14 days showed impaired object recognition and location memory and decreased activity in the open field, while those given 10 mg/kg did not show these alterations, suggesting dose-dependent effects of sub-anesthetic ketamine. |
Abstract
Ketamine is a noncompetitive antagonist of the NMDA-receptors, used as a dissociative anesthetic, presently included in the category of the psychoactive substances known as “club drugs”. Ketamine administration was associated with impaired working memory and increased psychopathological symptoms, but there is a lack of information regarding the effects of chronic sub-anesthetic doses. Adult Wistar rats were administered ketamine, 5 and 10 mg/kg twice daily, subcutaneously for 14 days. One week later, rats were tested in an object recognition/object location task and in the open field arena. There was altered performance in both the object recognition/location and in the open field tests by the group chronically exposed to the lower dose of ketamine. These animals displayed a decreased discrimination index (p<0.05) in the object recognition task, were unable to recognize the displacement of a familiar object and displayed decreased activity across open filed sessions. Importantly, these alterations were not observed in animals administered a higher dose of ketamine. Collectively, these results consistently show that chronic administration of ketamine in sub-anesthetic doses may lead to decreased habituation and inability to update spatial representations.
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 11
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Molecular Brain June 16, 2020
- Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice Translational Psychiatry September 15, 2015
- Ketamine use disorder: preclinical, clinical, and neuroimaging evidence to support proposed mechanisms of actions Intelligent Medicine March 7, 2022
- Prolonged ketamine therapy differentially rescues psychobehavioural deficits via modulation of nitro-oxidative stress and oxytocin receptors in the gut-brain-axis of chronically-stressed mice. Psychoneuroendocrinology December 1, 2023
- Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model. Schizophrenia Research April 1, 2025
and 6 more in the library
Cites 4
- Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry April 30, 2009
- Effects of repeated treatment of phencyclidine on cognition and gene expression in C57BL/6 mice. The International Journal of Neuropsychopharmacology March 2009
- Journey through the K-hole: phenomenological aspects of ketamine use. Drug and Alcohol Dependence March 19, 2008
- Modelling prefrontal cortex deficits in schizophrenia: implications for treatment. British Journal of Pharmacology March 2008