Repeated ketamine administration alters N -methyl- d -aspartic acid receptor subunit gene expression: Implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans
Ke Xu, Robert H Lipsky
Experimental Biology and Medicine February 1, 2015 DOI: 10.1177/1535370214549531 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Key findings | Argues that NMDA receptor subunit gene expression, particularly the GluN1 (NR1) subunit, may underlie ketamine-associated psychosis and cognitive deficits, and proposes that full sequencing of NMDA receptor genes could help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. |
Abstract
For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-d-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 13
- Long-term safety of ketamine and esketamine in treatment of depression Expert Opinion on Drug Safety April 13, 2022
- Repurposing potential of ketamine: Opportunities and challenges Indian Journal of Psychological Medicine January 17, 2020
- Ketamine induces multiple individually distinct whole-brain functional connectivity signatures. Elife April 17, 2024
- Rhynchophylline downregulates phosphorylated camp response element binding protein, nuclear receptor-related-1, and brain-derived neurotrophic factor expression in the hippocampus of ketamine-induced conditioned place preference rats Pharmacognosy Magazine 2018
- [Psychedelic and dissociative agents in psychiatry: challenges in the treatment]. Der Nervenarzt September 1, 2024
and 8 more in the library
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and 4 more in the library