{ "abstract": "Introduction\n\nMany military Veterans who experienced blast-related injuries during military service suffer from chronic cognitive and mental health problems. Women constitute more than 15% of active-duty U. S. military personnel and are the fastest-growing population of U. S. Veterans. For more than a decade, we have studied a rat model of repetitive low-level blast exposure designed to mimic the type of blast-related exposure that is common in military settings. Male rats develop chronic cognitive and post-traumatic stress disorder-related traits that appear in a delayed fashion and persist for more than 1 year after exposure. These traits can be reversed with a single dose of (2R,6R)-hydroxynorketamine [(2R,6R)-HNK]. This study aimed to determine whether female rats develop a similar set of neurobehavioral alterations.Methods\n\nTen-week-old female rats were exposed to 75.1 kPa blast overpressures delivered once per day for three consecutive days. We tested female rats behaviorally between 1 and 4 weeks after blast exposure and again at 28 and 29 weeks. Rats were tested in an elevated zero maze, light-dark emergence task, and novel object recognition task, as well as contextual and cued fear learning and a Barnes maze. We tested how females would respond to a single dose of 20 mg/kg (2R,6R)-HNK administered intraperitoneally.Results\n\nFollowing blast exposure, female rats developed chronic cognitive and behavioral traits. The full behavioral phenotype developed with a delay. Treatment with a single dose of (2R,6R)-HNK reversed behavioral changes in female rats, and beneficial effects on behavior were sustained for 4 weeks without additional drug administration. As in male rats, female rats showed elevated metabotropic glutamate receptor mGluR2. Elevations of mGluR2 were reversed by (2R,6R)-HNK treatment. Similar to male rats, the serotonin receptor 5-HT2AR was decreased in blast-injured female rats but levels were not affected by (2R,6R)-HNK treatment.Conclusion\n\nThese studies show that female rats develop a similar behavioral profile as previously observed in male rats using the same blast exposure conditions. They further support (2R,6R)-HNK as a promising therapeutic candidate for treatment of blast-induced neurobehavioral effects, even when administered after traits are well established.", "abstract_shown": true, "affiliations": [ "Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United States.", "Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.", "Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.", "General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United States.", "Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States.", "VA Sequencing Collaborations United for Research and Epidemiology (seqCURE), James J. Peters VA Medical Center, Bronx, NY, United States.", "The Bronx Veterans Medical Research Foundation (BVMRF), Bronx, NY, United States.", "Spinal Cord Damage Research Center, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United States.", "Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.", "Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.", "Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, NY, United States.", "Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, United States." ], "article_type": "research article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0, 1 ], "name": "Georgina Perez Garcia" }, { "affs": [ 0 ], "name": "Gissel M Perez" }, { "affs": [ 0, 2 ], "name": "Rita De Gasperi" }, { "affs": [ 2, 3 ], "name": "Miguel A Gama Sosa" }, { "affs": [ 0, 2, 4 ], "name": "Carolyn W Zhu" }, { "affs": [ 0 ], "name": "Serena Yeung" }, { "affs": [ 5, 6 ], "name": "Shahrukh Khalique" }, { "affs": [ 5, 6, 7, 8 ], "name": "Carlos A Toro" }, { "affs": [ 4, 9, 10 ], "name": "Patrick R Hof" }, { "affs": [ 1, 2, 4, 11 ], "name": "Gregory A Elder" } ], "bibtex": "https://research.draconitic.com/paper/3005p4rcsr173.bib", "cited_by": 0, "doi": "10.3389/fneur.2026.1830745", "fulltext_url": "https://europepmc.org/articles/PMC13683013", "id": "3005p4rcsr173", "issns": [ "1664-2295" ], "landing_url": "https://europepmc.org/article/MED/42908602", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "3203|Posttraumatic Stress Disorder Research" ] ], "openalex": "W7220859590", "pdf_url": "https://europepmc.org/articles/PMC13683013?pdf=render", "pmcid": "PMC13683013", "pmid": "42908602", "published": "2026-10-07", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/3005p4rcsr173.ris", "sources": [ { "first_seen": "2026-10-30T12:19:57Z", "native_id": "MED:42908602", "source": "europepmc", "url": "https://europepmc.org/article/MED/42908602" }, { "first_seen": "2026-10-30T12:20:16Z", "native_id": "10.3389/fneur.2026.1830745", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1830745/full" } ], "subjects": [ { "field": "medicine", "origin": "openalex:3203|Posttraumatic Stress Disorder Research", "subfield": "psychiatry" } ], "title": "Chronic post-traumatic stress disorder-related behavioral traits develop in female rats exposed to repetitive low-level blast injury and are reversible with (2R,6R)-hydroxynorketamine.", "title_text": "Chronic post-traumatic stress disorder-related behavioral traits develop in female rats exposed to repetitive low-level blast injury and are reversible with (2R,6R)-hydroxynorketamine.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:20:16Z", "url": "https://research.draconitic.com/paper/3005p4rcsr173", "venue": "Frontiers in neurology", "versions": [] }