{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:55:19Z","timestamp":1785902119452,"version":"3.56.0"},"reference-count":127,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thus, we summarized the existing preclinical literature examining effects of ketamine on fear extinction and its potential molecular mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2025.1546460","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T06:40:30Z","timestamp":1746081630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of ketamine on fear memory extinction: a review of preclinical literature"],"prefix":"10.3389","volume":"19","author":[{"given":"Martin","family":"Boese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennett","family":"Radford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke R.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1038\/s41386-022-01266-9","article-title":"Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial","volume":"47","author":"Abdallah","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17m","DOI":"10.4088\/JCP.17m11634","article-title":"Efficacy, safety, and durability of repeated ketamine infusions for comorbid posttraumatic stress disorder and treatment-resistant depression","volume":"79","author":"Albott","year":"2018","journal-title":"J. Clin. Psychiatry"},{"key":"B3","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.tips.2021.08.003","article-title":"Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics","volume":"42","author":"Aleksandrova","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1503\/jpn.160175","article-title":"Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism","volume":"42","author":"Aleksandrova","year":"2017","journal-title":"J. Psychiatry Neurosci."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.36131\/cnfioritieditore20240102","article-title":"Effectiveness of ketamine for the treatment of post-traumatic stress disorder - a systematic review and meta-analysis","author":"Almeida","year":"2024","journal-title":"Clin. Neuropsychiatry"},{"key":"B6","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"2022"},{"key":"B7","doi-asserted-by":"publisher","first-page":"103723","DOI":"10.1016\/j.mcn.2022.103723","article-title":"Ketamine attenuates the PTSD-like effect via regulation of glutamatergic signaling in the nucleus accumbens of mice","volume":"120","author":"Asim","year":"2022","journal-title":"Mol. Cell. Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s12264-019-00422-4","article-title":"Ketamine alleviates fear generalization through GluN2B-BDNF signaling in mice","volume":"36","author":"Asim","year":"2020","journal-title":"Neurosci. Bull."},{"key":"B9","doi-asserted-by":"publisher","first-page":"105044","DOI":"10.1016\/j.neuint.2021.105044","article-title":"Ketamine for post-traumatic stress disorders and it's possible therapeutic mechanism","volume":"146","author":"Asim","year":"2021","journal-title":"Neurochem. Int."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e15698","DOI":"10.1371\/journal.pone.0015698","article-title":"Pavlovian fear conditioning activates a common pattern of neurons in the lateral amygdala of individual brains","volume":"6","author":"Bergstrom","year":"2011","journal-title":"PLoS ONE"},{"key":"B11","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1007\/s10548-012-0266-6","article-title":"Neurons activated during fear memory consolidation and reconsolidation are mapped to a common and new topography in the lateral amygdala","volume":"26","author":"Bergstrom","year":"2013","journal-title":"Brain Topogr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0006-3223(99)00230-9","article-title":"Antidepressant effects of ketamine in depressed patients","volume":"47","author":"Berman","year":"2000","journal-title":"Biol. Psychiatry"},{"key":"B13","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1101\/lm.78804","article-title":"Context and behavioral processes in extinction","volume":"11","author":"Bouton","year":"2004","journal-title":"Learn. Mem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1503\/jpn.170021","article-title":"Mindfulness-based treatments for posttraumatic stress disorder: a review of the treatment literature and neurobiological evidence","volume":"43","author":"Boyd","year":"2018","journal-title":"J. Psychiatry Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"17647","DOI":"10.51894\/001c.17647","article-title":"Does peritraumatic ketamine reduce symptoms of post-traumatic stress disorder?","volume":"5","author":"Brodeur","year":"2020","journal-title":"Spartan Med. Res. J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"7173","DOI":"10.3390\/ijms21197173","article-title":"Effects of ketamine on rodent fear memory","volume":"21","author":"Choi","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s11920-020-1140-y","article-title":"Gender- and sex-based contributors to sex differences in PTSD","volume":"22","author":"Christiansen","year":"2020","journal-title":"Curr. Psychiatry Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1126\/science.1195298","article-title":"Calcium-permeable AMPA receptor dynamics mediate fear memory erasure","volume":"330","author":"Clem","year":"2010","journal-title":"Science"},{"key":"B19","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1177\/0269881117748903","article-title":"The effect of ketamine on the consolidation and extinction of contextual fear memory","volume":"32","author":"Clifton","year":"2018","journal-title":"J. Psychopharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1097\/00000542-197310000-00003","article-title":"Distribution in the brain and metabolism of ketamine in the rat after intravenous administration","volume":"39","author":"Cohen","year":"1973","journal-title":"Anesthesiology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1177\/0269881116650087","article-title":"Prediction error, ketamine and psychosis: an updated model","volume":"30","author":"Corlett","year":"2016","journal-title":"J. Psychopharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e3002679","DOI":"10.1371\/journal.pbio.3002679","article-title":"Dominantactivities of fear engram cells in the dorsal dentate gyrus underlie fear generalization in mice","volume":"22","author":"Cui","year":"2024","journal-title":"PLoS Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/0091-3057(94)90506-1","article-title":"Glutamate antagonists have different effects on spontaneous locomotor activity in rats","volume":"48","author":"Danysz","year":"1994","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B24","doi-asserted-by":"publisher","first-page":"463","DOI":"10.31887\/DCNS.2011.13.4\/mdavis","article-title":"NMDA receptors and fear extinction: implications for cognitive behavioral therapy","volume":"13","author":"Davis","year":"2011","journal-title":"Dialogues Clin. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/S0166-2236(99)01438-1","article-title":"Stress and cognition: are corticosteroids good or bad guys?","volume":"22","author":"de Kloet","year":"1999","journal-title":"Trends Neurosci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nrn.2016.155","article-title":"Stress, glucocorticoids and memory: implications for treating fear-related disorders","volume":"18","author":"de Quervain","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"108710","DOI":"10.1016\/j.neuropharm.2021.108710","article-title":"AMPA receptor trafficking and LTP: Carboxy-termini, amino-termini and TARPs","volume":"197","author":"Diaz-Alonso","year":"2021","journal-title":"Neuropharmacology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1038\/s41386-023-01606-3","article-title":"Long term structural and functional neural changes following a single infusion of Ketamine in PTSD","volume":"48","author":"Duek","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/j.1460-9568.2004.03824.x","article-title":"Activation of extracellular signal-regulated kinase- mitogen-activated protein kinase cascade in the amygdala is required for memory reconsolidation of auditory fear conditioning","volume":"21","author":"Duvarci","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1001\/jamapsychiatry.2014.62","article-title":"Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial","volume":"71","author":"Feder","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"B31","doi-asserted-by":"publisher","first-page":"652636","DOI":"10.3389\/fnbeh.2021.652636","article-title":"Systematic review and methodological considerations for the use of single prolonged stress and fear extinction retention in rodents","volume":"15","author":"Ferland-Beckham","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1146665","DOI":"10.3389\/fnsyn.2023.1146665","article-title":"Memory retrieval, reconsolidation, and extinction: exploring the boundary conditions of post-conditioning cue exposure","volume":"15","author":"Ferrara","year":"2023","journal-title":"Front. Synaptic Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1176\/appi.focus.20230006","article-title":"Ketamine for treatment of posttraumatic stress disorder: state of the field","volume":"21","author":"Fremont","year":"2023","journal-title":"Focus"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2016.12.026","article-title":"Ketamine accelerates fear extinction via mTORC1 signaling","volume":"100","author":"Girgenti","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"669","DOI":"10.3390\/ph17060669","article-title":"Ketamine's amelioration of fear extinction in adolescent male mice is associated with the activation of the hippocampal Akt-mTOR-GluA1 pathway","volume":"17","author":"Glavonic","year":"2024","journal-title":"Pharmaceuticals"},{"key":"B36","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1002\/jnr.25017","article-title":"Hallucinogenic drugs and their potential for treating fear-related disorders: through the lens of fear extinction","volume":"100","author":"Glavonic","year":"2022","journal-title":"J. Neurosci. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1177\/0269881117705089","article-title":"Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders","volume":"31","author":"Glue","year":"2017","journal-title":"J. Psychopharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1007\/s00213-024-06571-3","article-title":"The role of mGluR5 on the therapeutic effects of ketamine in Wistar rats","volume":"241","author":"Gokalp","year":"2024","journal-title":"Psychopharmacology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1007\/s00127-016-1208-5","article-title":"The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III","volume":"51","author":"Goldstein","year":"2016","journal-title":"Soc. Psychiatry Psychiatr. Epidemiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.biopsych.2009.04.017","article-title":"D-cycloserine facilitation of fear extinction and exposure-based therapy might rely on lower-level, automatic mechanisms","volume":"66","author":"Grillon","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"B41","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.pbb.2015.10.013","article-title":"Ketamine administration diminishes operant responding but does not impair conditioned fear","volume":"139","author":"Groeber Travis","year":"2015","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B42","unstructured":"Harpaz-Rotem\n              I.\n            \n          \n          Combining neurobiology and new learning: ketamine and prolonged exposure: a potential rapid treatment for post-traumatic stress disorder (PTSD)\n          \n          2022"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1097\/ALN.0b013e31821c120e","article-title":"Propofol enhances memory formation via an interaction with the endocannabinoid system","volume":"114","author":"Hauer","year":"2011","journal-title":"Anesthesiology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1460-9568.2010.07101.x","article-title":"Neuronal circuits of fear extinction","volume":"31","author":"Herry","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1006\/nlme.1996.0032","article-title":"Retrograde enhancement of human kinesthetic memory by alcohol: consolidation or protection against interference?","volume":"65","author":"Hewitt","year":"1996","journal-title":"Neurobiol. Learn. Mem"},{"key":"B46","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1213\/ANE.0000000000004327","article-title":"Ketamine administration during hospitalization is not associated with posttraumatic stress disorder outcomes in military combat casualties: a matched cohort study","volume":"130","author":"Highland","year":"2020","journal-title":"Anesth. Analg."},{"key":"B47","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.brainresbull.2006.01.010","article-title":"Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity","volume":"69","author":"Imre","year":"2006","journal-title":"Brain Res. Bull."},{"key":"B48","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/s00213-018-5068-4","article-title":"Microtopography of fear memory consolidation and extinction retrieval within prefrontal cortex and amygdala","volume":"236","author":"Jacques","year":"2019","journal-title":"Psychopharmacology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1002\/hipo.20331","article-title":"Hippocampal involvement in contextual modulation of fear extinction","volume":"17","author":"Ji","year":"2007","journal-title":"Hippocampus"},{"key":"B50","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.cell.2011.10.009","article-title":"Molecular mechanisms of fear learning and memory","volume":"147","author":"Johansen","year":"2011","journal-title":"Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3389\/fncel.2017.00100","article-title":"The combination of long-term ketamine and extinction training contributes to fear erasure by bdnf methylation","volume":"11","author":"Ju","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.euroneuro.2013.08.007","article-title":"Immediate ketamine treatment does not prevent posttraumatic stress responses in an animal model for PTSD","volume":"24","author":"Juven-Wetzler","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1353383","DOI":"10.1080\/20008198.2017.1353383","article-title":"Trauma and PTSD in the WHO World Mental Health Surveys","volume":"8","author":"Kessler","year":"2017","journal-title":"Eur. J. Psychotraumatol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1101\/lm.024356.111","article-title":"Single prolonged stress disrupts retention of extinguished fear in rats","volume":"19","author":"Knox","year":"2012","journal-title":"Learn. Mem."},{"key":"B55","volume-title":"Antidepressant-like Effects of Ketamine on Fear Conditioning and Extinction","author":"Kulyk","year":"2017"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1177\/0269881118780013","article-title":"The effect of route of administration on the enantioselective pharmacokinetics of ketamine and norketamine in rats","volume":"32","author":"Le Nedelec","year":"2018","journal-title":"J. Psychopharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1016\/j.neuron.2024.06.026","article-title":"Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells","volume":"112","author":"Li","year":"2024","journal-title":"Neuron"},{"key":"B58","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/S0306-4530(97)00044-9","article-title":"Stress-restress: effects on ACTH and fast feedback","volume":"22","author":"Liberzon","year":"1997","journal-title":"Psychoneuroendocrinology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1001\/jamapsychiatry.2016.3783","article-title":"World mental health survey association of DSM-IV posttraumatic stress disorder with traumatic experience type and history in the world health organization world mental health surveys","volume":"74","author":"Liu","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"B60","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1192\/bjp.2023.79","article-title":"Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial","volume":"223","author":"Loo","year":"2023","journal-title":"Br. J. Psychiatry"},{"key":"B61","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/S0022-3565(25)30447-7","article-title":"Biodisposition of ketamine in the rat: self-induction of metabolism","volume":"196","author":"Marietta","year":"1976","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B62","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.euroneuro.2019.03.013","article-title":"Sex-dependent changes in ketamine-induced locomotor activity and ketamine pharmacokinetics in preweanling, adolescent, and adult rats","volume":"29","author":"McDougall","year":"2019","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1126\/science.287.5451.248","article-title":"Memory\u2013a century of consolidation","volume":"287","author":"McGaugh","year":"2000","journal-title":"Science"},{"key":"B64","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0959-4388(02)00306-9","article-title":"Role of adrenal stress hormones in forming lasting memories in the brain","volume":"12","author":"McGaugh","year":"2002","journal-title":"Curr. Opin. Neurobiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"S195","DOI":"10.1097\/TA.0b013e318160ba1d","article-title":"The correlation between ketamine and posttraumatic stress disorder in burned service members","volume":"64","author":"McGhee","year":"2008","journal-title":"J Trauma"},{"key":"B66","doi-asserted-by":"publisher","first-page":"41","DOI":"10.7205\/MILMED-D-13-00481","article-title":"The intraoperative administration of ketamine to burned U.S. service members does not increase the incidence of post-traumatic stress disorder","volume":"179","author":"McGhee","year":"2014","journal-title":"Mil. Med"},{"key":"B67","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.biopsych.2023.06.030","article-title":"Traumatic brain injury-induced fear generalization in mice involves hippocampal memory trace dysfunction and is alleviated by (R,S)-ketamine","volume":"95","author":"McGowan","year":"2024","journal-title":"Biol. Psychiatry"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1038\/npp.2017.19","article-title":"Prophylactic ketamine attenuates learned fear","volume":"42","author":"McGowan","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1046\/j.1460-9568.2002.02188.x","article-title":"Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance in rats","volume":"16","author":"McIntyre","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1037\/tra0000978","article-title":"The effects of web-prolonged exposure among military personnel and veterans with posttraumatic stress disorder","volume":"13","author":"McLean","year":"2021","journal-title":"Psychol. Trauma"},{"key":"B71","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1515\/revneuro-2019-0090","article-title":"The neurophysiology of ketamine: an integrative review","volume":"31","author":"McMillan","year":"2020","journal-title":"Rev. Neurosci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/milmed\/usac014","article-title":"Is prehospital ketamine associated with a change in the prognosis of PTSD?","volume":"13","author":"Melcer","year":"2022","journal-title":"Mil. Med"},{"key":"B73","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.mcna.2022.04.003","article-title":"Post-traumatic stress disorder","volume":"107","author":"Merians","year":"2023","journal-title":"Med. Clin. North Am."},{"key":"B74","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/nature01138","article-title":"Neurons in medial prefrontal cortex signal memory for fear extinction","volume":"420","author":"Milad","year":"2002","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev.psych.121208.131631","article-title":"Fear extinction as a model for translational neuroscience: ten years of progress","volume":"63","author":"Milad","year":"2012","journal-title":"Annu. Rev. Psychol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1111\/anae.14079","article-title":"A retrospective study of ketamine administration and the development of acute or post-traumatic stress disorder in 274 war-wounded soldiers","volume":"72","author":"Mion","year":"2017","journal-title":"Anaesthesia"},{"key":"B77","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1111\/cns.12099","article-title":"Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings)","volume":"19","author":"Mion","year":"2013","journal-title":"CNS Neurosci. Ther."},{"key":"B78","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1523\/JNEUROSCI.17-08-02921.1997","article-title":"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","volume":"17","author":"Moghaddam","year":"1997","journal-title":"J. Neurosci."},{"key":"B79","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1126\/science.1167975","article-title":"Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories","volume":"324","author":"Monfils","year":"2009","journal-title":"Science"},{"key":"B80","doi-asserted-by":"publisher","first-page":"107362","DOI":"10.1016\/j.nlm.2020.107362","article-title":"Ketamine anesthesia enhances fear memory consolidation via noradrenergic activation in the basolateral amygdala","volume":"178","author":"Morena","year":"2021","journal-title":"Neurobiol. Learn. Mem."},{"key":"B81","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1037\/0735-7044.109.4.681","article-title":"Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats","volume":"109","author":"Morgan","year":"1995","journal-title":"Behav. Neurosci"},{"key":"B82","doi-asserted-by":"publisher","first-page":"43","DOI":"10.12703\/P7-43","article-title":"The problem of dropout from \u201cgold standard\u201d PTSD therapies","volume":"7","author":"Najavits","year":"2015","journal-title":"F1000Prime Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"108936","DOI":"10.1016\/j.neuropharm.2021.108936","article-title":"CYP 450 enzymes influence (R,S)-ketamine brain delivery and its antidepressant activity","volume":"206","author":"Nguyen","year":"2022","journal-title":"Neuropharmacology"},{"key":"B84","doi-asserted-by":"publisher","first-page":"5729","DOI":"10.1017\/S0033291722002951","article-title":"Irremediability in psychiatric euthanasia: examining the objective standard","volume":"53","author":"Nicolini","year":"2023","journal-title":"Psychol. Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.biopsych.2008.01.012","article-title":"A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy","volume":"63","author":"Norberg","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"B86","doi-asserted-by":"publisher","first-page":"100468","DOI":"10.1016\/j.ynstr.2022.100468","article-title":"Adjunct treatment with ketamine enhances the therapeutic effects of extinction learning after chronic unpredictable stress","volume":"19","author":"Paredes","year":"2022","journal-title":"Neurobiol. Stress"},{"key":"B87","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/BF00427653","article-title":"Retrograde enhancement of human memory with alcohol","volume":"69","author":"Parker","year":"1980","journal-title":"Psychopharmacology"},{"key":"B88","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/s41386-019-0570-x","article-title":"Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression","volume":"45","author":"Phillips","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"B89","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1037\/0735-7044.106.2.274","article-title":"Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning","volume":"106","author":"Phillips","year":"1992","journal-title":"Behav. Neurosci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.bbapap.2018.03.006","article-title":"d-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: a pilot study","volume":"1866","author":"Pradhan","year":"2018","journal-title":"Biochim. Biophys. Acta Proteins Proteom"},{"key":"B91","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4103\/2542-3932.211589","article-title":"Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic efects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial","volume":"2","author":"Pradhan","year":"2017","journal-title":"Asia Pac. J. Clin. Trials nerv. Syst. Dis."},{"key":"B92","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/s11920-015-0655-0","article-title":"Prevention of post-traumatic stress disorder after trauma: current evidence and future directions","volume":"18","author":"Qi","year":"2016","journal-title":"Curr. Psychiatry Rep."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.3390\/ijms23031922","article-title":"Enhanced fear memories and altered brain glucose metabolism ((18)F-FDG-PET) following subanesthetic intravenous ketamine infusion in Female Sprague-Dawley rats","volume":"23","author":"Radford","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B94","doi-asserted-by":"publisher","first-page":"173042","DOI":"10.1016\/j.pbb.2020.173042","article-title":"Sex-related differences in intravenous ketamine effects on dissociative stereotypy and antinociception in male and female rats","volume":"199","author":"Radford","year":"","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B95","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41398-018-0310-8","article-title":"Enhanced fear memories and brain glucose metabolism ((18)F-FDG-PET) following sub-anesthetic intravenous ketamine infusion in Sprague-Dawley rats","volume":"8","author":"Radford","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"B96","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.pbb.2016.12.014","article-title":"Dose-response characteristics of intravenous ketamine on dissociative stereotypy, locomotion, sensorimotor gating, and nociception in male Sprague-Dawley rats","volume":"153","author":"Radford","year":"2017","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B97","doi-asserted-by":"publisher","first-page":"112259","DOI":"10.1016\/j.bbr.2019.112259","article-title":"Association between intravenous ketamine-induced stress hormone levels and long-term fear memory renewal in Sprague-Dawley rats","volume":"378","author":"Radford","year":"","journal-title":"Behav. Brain Res."},{"key":"B98","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.jad.2024.10.025","article-title":"Prevalence and factors associated with polypharmacy in military and veteran populations: a systematic review and meta-analysis","volume":"369","author":"Raut","year":"2024","journal-title":"J. Affect. Disord."},{"key":"B99","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.jpsychires.2022.03.045","article-title":"Effects of propranolol on the modification of trauma memory reconsolidation in PTSD patients: a systematic review and meta-analysis","volume":"150","author":"Raut","year":"","journal-title":"J. Psychiatr. Res."},{"key":"B100","doi-asserted-by":"publisher","first-page":"108195","DOI":"10.1016\/j.pharmthera.2022.108195","article-title":"Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation","volume":"239","author":"Raut","year":"","journal-title":"Pharmacol. Ther."},{"key":"B101","doi-asserted-by":"publisher","first-page":"261","DOI":"10.3758\/BF03194062","article-title":"Retrograde facilitation under midazolam: the role of general and specific interference","volume":"14","author":"Reder","year":"2007","journal-title":"Psychon. Bull. Rev"},{"key":"B102","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41398-021-01685-0","article-title":"(R,S)-ketamine and (2R,6R)-hydroxynorketamine differentially affect memory as a function of dosing frequency","volume":"11","author":"Riggs","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"B103","doi-asserted-by":"publisher","first-page":"8161","DOI":"10.1523\/JNEUROSCI.2574-04.2004","article-title":"Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala","volume":"24","author":"Roozendaal","year":"2004","journal-title":"J. Neurosci."},{"key":"B104","article-title":"High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans","author":"Ross","year":"2019","journal-title":"Ann. Clin. Psychiatry"},{"key":"B105","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/s41398-022-02116-4","article-title":"The role of BDNF in mediating the prophylactic effects of (R,S)-ketamine on fear generalization and extinction","volume":"12","author":"Ryan","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"B106","doi-asserted-by":"publisher","first-page":"759626","DOI":"10.3389\/fphar.2022.759626","article-title":"Acute ketamine facilitates fear memory extinction in a rat model of PTSD along with restoring glutamatergic alterations and dendritic atrophy in the prefrontal cortex","volume":"13","author":"Sala","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1124\/jpet.118.251652","article-title":"Sex differences in the pharmacokinetics of low-dose ketamine in plasma and brain of male and female rats","volume":"367","author":"Saland","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B108","doi-asserted-by":"publisher","first-page":"635879","DOI":"10.3389\/fnsyn.2021.635879","article-title":"Dopamine in fear extinction","volume":"13","author":"Salinas-Hernandez","year":"2021","journal-title":"Front. Synaptic Neurosci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"78970","DOI":"10.1155\/2007\/78970","article-title":"Stress and memory: behavioral effects and neurobiological mechanisms","volume":"2007","author":"Sandi","year":"2007","journal-title":"Neural. Plast."},{"key":"B110","doi-asserted-by":"publisher","first-page":"107402","DOI":"10.1016\/j.pharmthera.2019.107402","article-title":"Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders","volume":"204","author":"Sartori","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"B111","doi-asserted-by":"publisher","first-page":"RC96","DOI":"10.1523\/JNEUROSCI.20-18-j0003.2000","article-title":"Memory consolidation of auditory pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala","volume":"20","author":"Schafe","year":"2000","journal-title":"J. Neurosci"},{"key":"B112","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nature08637","article-title":"Preventing the return of fear in humans using reconsolidation update mechanisms","volume":"463","author":"Schiller","year":"2010","journal-title":"Nature"},{"key":"B113","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1177\/0269881107082481","article-title":"Ketamine aggravates symptoms of acute stress disorder in a naturalistic sample of accident victims","volume":"22","author":"Schonenberg","year":"2008","journal-title":"J. Psychopharmacol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"107569","DOI":"10.1016\/j.cct.2024.107569","article-title":"Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: a randomized controlled trial protocol","volume":"143","author":"Shiroma","year":"2024","journal-title":"Contemp. Clin. Trials"},{"key":"B115","doi-asserted-by":"publisher","first-page":"20l","DOI":"10.4088\/JCP.20l13406","article-title":"A proof-of-concept study of subanesthetic intravenous ketamine combined with prolonged exposure therapy among veterans with posttraumatic stress disorder","volume":"81","author":"Shiroma","year":"2020","journal-title":"J. Clin. Psychiatry"},{"key":"B116","doi-asserted-by":"publisher","first-page":"109418","DOI":"10.1016\/j.neuropharm.2023.109418","article-title":"Alleviating anxiety and taming trauma: novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder","volume":"226","author":"Singewald","year":"2023","journal-title":"Neuropharmacology"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002795.pub2","article-title":"Pharmacotherapy for post traumatic stress disorder (PTSD)","author":"Stein","year":"2006","journal-title":"Cochrane Database Syst. Rev"},{"key":"B118","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1080\/14737175.2019.1640604","article-title":"Esketamine for treatment resistant depression","volume":"19","author":"Swainson","year":"2019","journal-title":"Expert Rev. Neurother."},{"key":"B119","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jad.2023.11.023","article-title":"Comparative efficacy, tolerability and acceptability of intravenous racemic ketamine with intranasal esketamine, aripiprazole and lithium as augmentative treatments for treatment-resistant unipolar depression: a systematic review and network meta-analysis","volume":"346","author":"Terao","year":"2024","journal-title":"J. Affect. Disord."},{"key":"B120","doi-asserted-by":"publisher","first-page":"1378612","DOI":"10.3389\/fphar.2024.1378612","article-title":"Non-competitive NMDA antagonist MK-801 prevents memory reconsolidation impairment caused by protein synthesis inhibitors in young chicks","volume":"15","author":"Tiunova","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/nn.2350","article-title":"Cellular and systems mechanisms of memory strength as a constraint on auditory fear reconsolidation","volume":"12","author":"Wang","year":"2009","journal-title":"Nat. Neurosci."},{"key":"B122","doi-asserted-by":"publisher","first-page":"112342","DOI":"10.1016\/j.bbr.2019.112342","article-title":"Ketamine reverses the impaired fear memory extinction and accompanied depressive-like behaviors in adolescent mice","volume":"379","author":"Wei","year":"2020","journal-title":"Behav. Brain Res."},{"key":"B123","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00213-018-5111-5","article-title":"Sound check, stage design and screen plot - how to increase the comparability of fear conditioning and fear extinction experiments","volume":"236","author":"Wotjak","year":"2019","journal-title":"Psychopharmacology"},{"key":"B124","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/B978-0-12-802381-5.00036-1","author":"Wynn","year":"2017"},{"key":"B125","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/0031-9384(73)90236-9","article-title":"Ketamine anesthesia for rats","volume":"10","author":"Youth","year":"1973","journal-title":"Physiol. Behav."},{"key":"B126","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/mp.2017.255","article-title":"Mechanisms of ketamine action as an antidepressant","volume":"23","author":"Zanos","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"B127","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.3758\/s13415-023-01118-z","article-title":"Age-related impairment in fear memory extinction is restored by ketamine in middle-aged mice","volume":"23","author":"Zhao","year":"2023","journal-title":"Cogn. Affect. Behav. Neurosci."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1546460\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T20:50:50Z","timestamp":1746132650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1546460\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":127,"alternative-id":["10.3389\/fnins.2025.1546460"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2025.1546460","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]},"article-number":"1546460"}}