Effects of ketamine on fear memory extinction: a review of preclinical literature.
Martin Boese, Rina Y. Berman, Kennett D. Radford, Luke R Johnson, Kwang H. Choi
Frontiers in Neuroscience 2025 DOI: 10.3389/fnins.2025.1546460 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Fear memory Molecular mechanism Translational research PTSD Treatment Fear extinction research Ketamine therapy Psychopharmacology Trauma therapy |
| Citations | 5 |
| Key findings | Ketamine's effects on fear extinction in preclinical studies are inconsistent, varying by dosage, route, and timing of administration. |
Abstract
Ketamine, a multimodal dissociative anesthetic, is widely used as a trauma analgesic in emergency situations. Ketamine is also used to treat psychiatric disorders due to its broad application potential, including treatment-resistant major depression. However, its impacts on the development of post-traumatic stress disorder (PTSD) and its potential as a treatment for PTSD are controversial. PTSD is marked by persistent and intrusive memories of traumatic event(s) and re-experiencing of the traumatic memories when exposed to trauma-related stimuli. Individuals with PTSD are often treated with prolonged exposure therapy (PE), in which they are gradually exposed to stimuli that remind them of the previous traumatic memory. If successful, they may learn that the previously traumatic stimuli are no longer threatening, a process known as fear extinction. Although fear extinction can be studied in laboratory animals, previous preclinical literature on the effects of ketamine on fear extinction has been inconsistent. Thus, we summarized the existing preclinical literature examining effects of ketamine on fear extinction and its potential molecular mechanisms. Studies found that ketamine may enhance, impair, have no effect, or have mixed effects on fear extinction. These discrepancies may be attributed to differences in dosage, route, and timing of ketamine administration. We conclude the review with recommendations for future research on ketamine and PTSD such as the inclusion of more female subjects, clinically relevant doses and routes of ketamine administration, and more comprehensive behavioral assays that are relevant to PTSD in humans to enhance translation between preclinical and clinical research.
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 2
Cites 35
- 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 Journal of Neuroscience April 15, 1997
- 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
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
and 30 more in the library