Effects of NMDA antagonists ketamine, methoxetamine and phencyclidine on the odor span test of working memory in rats
Michael Mathews, R. N. Mead, M. Galizio
Experimental and Clinical Psychopharmacology February 1, 2018 DOI: 10.1037/pha0000158 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Population | Rodents (rats) |
| Interventions | Phencyclidine Ketamine Methoxetamine |
| Topics | Esketamine Ketamine |
| Key findings | PCP and MXE impaired odor span accuracy at high memory loads without affecting simple discrimination, while ketamine's effects were less selective. |
Abstract
The glutamate hypothesis proposes that N-Methyl-D-aspartate (NMDA) receptor hypofunction underlies cognitive and perhaps other schizophrenic symptoms. The present study used the odor span task to assess the effects of NMDA antagonists on remembering multiple stimuli in rodents. This task uses an incrementing nonmatching-to-sample procedure in which responses to a new olfactory stimulus are reinforced on each trial, whereas responses to previously presented stimuli are not. NMDA antagonists have been associated with memory impairments in a variety of animal models; however, there are inconsistencies across different NMDA antagonists and tasks used. The current study compared the acute effects of phencyclidine (PCP), ketamine (KET), and the novel NMDA antagonist methoxetamine (MXE) on responding in the odor span task and a simple discrimination control task. PCP and MXE impaired odor span accuracy at doses that did not impair simple discrimination in most rats; however, the effects of KET were less selective. Within-session analyses indicated that the effects of PCP and MXE depended on the number of stimuli to remember, that is, impairment only occurred when the memory load was relatively high. These effects of PCP and MXE were consistent with the hypothesis that NMDA antagonists may interfere with working memory, but the basis for less selective results with KET are unclear.
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 5
- Dorsolateral Prefrontal Cortex Impairment in Methoxetamine-Induced Psychosis: An 18F-FDG PET/CT Case Study Journal of Psychoactive Drugs February 9, 2019
- 3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report. Pharmaceuticals March 31, 2024
- New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat. Experimental Neurology November 1, 2021
- The Involvement of the Serotonergic System in Ketamine and Fluoxetine Combination-induced Cognitive Impairments in Mice. The Eurasian journal of medicine June 1, 2024
- The novel psychoactive substance methoxetamine induces persistent behavioral abnormalities and neurotoxicity in rats Neuropharmacology 2019
Cites 6
- The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One June 14, 2016
- Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings Behavioural Pharmacology September 1, 2016
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- The ketamine analogue methoxetamine generalizes to ketamine discriminative stimulus in rats. Behavioural Pharmacology April 1, 2016
- The novel ketamine analog methoxetamine produces dissociative-like behavioral effects in rodents. Psychopharmacology April 1, 2016
and 1 more in the library