Effects of ketamine on fear memory extinction: a review of preclinical literature
IntroductionKetamine, 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 developme...
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Frontiers Media S.A.
2025-04-01
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| author | Martin Boese Rina Berman Kennett Radford Luke R. Johnson Luke R. Johnson Luke R. Johnson Kwang Choi Kwang Choi Kwang Choi |
| author_facet | Martin Boese Rina Berman Kennett Radford Luke R. Johnson Luke R. Johnson Luke R. Johnson Kwang Choi Kwang Choi Kwang Choi |
| author_sort | Martin Boese |
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| description | IntroductionKetamine, 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.MethodsThus, we summarized the existing preclinical literature examining effects of ketamine on fear extinction and its potential molecular mechanisms.ResultsStudies 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.DiscussionWe 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. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-d3ec02c7a0e54b4ebb60c0c2a7cd6e8e2025-08-20T03:53:42ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-04-011910.3389/fnins.2025.15464601546460Effects of ketamine on fear memory extinction: a review of preclinical literatureMartin Boese0Rina Berman1Kennett Radford2Luke R. Johnson3Luke R. Johnson4Luke R. Johnson5Kwang Choi6Kwang Choi7Kwang Choi8Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, Bethesda, MD, United StatesCenter for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD, United StatesWalter Reed National Military Medical Center, Bethesda, MD, United StatesCenter for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD, United StatesSchool of Psychological Sciences, College of Health and Medicine, University of Tasmania, Hobart, TAS, AustraliaDepartment of Psychiatry, Uniformed Services University, Bethesda, MD, United StatesDaniel K. Inouye Graduate School of Nursing, Uniformed Services University, Bethesda, MD, United StatesCenter for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD, United StatesDepartment of Psychiatry, Uniformed Services University, Bethesda, MD, United StatesIntroductionKetamine, 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.MethodsThus, we summarized the existing preclinical literature examining effects of ketamine on fear extinction and its potential molecular mechanisms.ResultsStudies 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.DiscussionWe 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.https://www.frontiersin.org/articles/10.3389/fnins.2025.1546460/fullketaminefear memoryposttraumatic stress disorder (PTSD)fear extinctioncognitive behavioral therapy (CBT)review |
| spellingShingle | Martin Boese Rina Berman Kennett Radford Luke R. Johnson Luke R. Johnson Luke R. Johnson Kwang Choi Kwang Choi Kwang Choi Effects of ketamine on fear memory extinction: a review of preclinical literature Frontiers in Neuroscience ketamine fear memory posttraumatic stress disorder (PTSD) fear extinction cognitive behavioral therapy (CBT) review |
| title | Effects of ketamine on fear memory extinction: a review of preclinical literature |
| title_full | Effects of ketamine on fear memory extinction: a review of preclinical literature |
| title_fullStr | Effects of ketamine on fear memory extinction: a review of preclinical literature |
| title_full_unstemmed | Effects of ketamine on fear memory extinction: a review of preclinical literature |
| title_short | Effects of ketamine on fear memory extinction: a review of preclinical literature |
| title_sort | effects of ketamine on fear memory extinction a review of preclinical literature |
| topic | ketamine fear memory posttraumatic stress disorder (PTSD) fear extinction cognitive behavioral therapy (CBT) review |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1546460/full |
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