{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:40:41Z","timestamp":1790487641727,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TriService Nursing Research Program","award":["N18-B08"],"award-info":[{"award-number":["N18-B08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although women and men are equally likely to receive ketamine following traumatic injury, little is known regarding sex-related differences in the impact of ketamine on traumatic memory. We previously reported that subanesthetic doses of an intravenous (IV) ketamine infusion following fear conditioning impaired fear extinction and altered regional brain glucose metabolism (BGluM) in male rats. Here, we investigated the effects of IV ketamine infusion on fear memory, stress hormone levels, and BGluM in female rats. Adult female Sprague\u2013Dawley rats received a single IV ketamine infusion (0, 2, 10, or 20 mg\/kg, over a 2-h period) following auditory fear conditioning (three pairings of tone and footshock). Levels of plasma stress hormones, corticosterone (CORT) and progesterone, were measured after the ketamine infusion. Two days after ketamine infusion, fear memory retrieval, extinction, and renewal were tested over a three-day period. The effects of IV ketamine infusion on BGluM were determined using 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG-PET) and computed tomography (CT). The 2 and 10 mg\/kg ketamine infusions reduced locomotor activity, while 20 mg\/kg infusion produced reduction (first hour) followed by stimulation (second hour) of activity. The 10 and 20 mg\/kg ketamine infusions significantly elevated plasma CORT and progesterone levels. All three doses enhanced fear memory retrieval, impaired fear extinction, and enhanced cued fear renewal in female rats. Ketamine infusion produced dose-dependent effects on BGluM in fear- and stress-sensitive brain regions of female rats. The current findings indicate that subanesthetic doses of IV ketamine produce robust effects on the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis and brain energy utilization that may contribute to enhanced fear memory observed in female rats.<\/jats:p>","DOI":"10.3390\/ijms23031922","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:37:48Z","timestamp":1644363468000},"page":"1922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Enhanced Fear Memories and Altered Brain Glucose Metabolism (18F-FDG-PET) following Subanesthetic Intravenous Ketamine Infusion in Female Sprague\u2013Dawley Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Kennett D.","family":"Radford","sequence":"first","affiliation":[{"name":"Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0517-4224","authenticated-orcid":false,"given":"Rina Y.","family":"Berman","sequence":"additional","affiliation":[{"name":"Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"Biomedical Research Imaging Core (BRIC), Department of Radiology and Radiological Sciences, Uniformed Services University, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-1909","authenticated-orcid":false,"given":"Haley F.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2884-4996","authenticated-orcid":false,"given":"Kwang H.","family":"Choi","sequence":"additional","affiliation":[{"name":"Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, Bethesda, MD 20814, USA"},{"name":"Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA"},{"name":"Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA"},{"name":"Department of Psychiatry, F. E. H\u00e9bert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1365-2044.2008.05835.x","article-title":"Anaesthesia in haemodynamically compromised emergency patients: Does ketamine represent the best choice of induction agent?","volume":"64","author":"Morris","year":"2009","journal-title":"Anaesthesia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1001\/archpsyc.1994.03950030035004","article-title":"Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses","volume":"51","author":"Krystal","year":"1994","journal-title":"Arch. Gen. 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