{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:24:56Z","timestamp":1792794296229,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"Miami University","doi-asserted-by":"publisher","award":["1R21AA028602-01A1"],"award-info":[{"award-number":["1R21AA028602-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. Patients diagnosed with post-traumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with individuals exposed to early adverse experiences and women having increased vulnerability for diagnoses; however, the mechanisms of this increased vulnerability remain unknown. PTSD involves a complex network of highly interconnected brain regions, including the bed nucleus of the stria terminalis (BNST). Serotonin (5-HT) release into the BNST yields an increased expression of both fear and anxiety, specifically through 5-HT2C receptor signaling. The present experiment addressed whether 5-HT2C receptor signaling in the BNST is necessary for the acquisition of early-life stress (ELS)-induced enhancements in adult contextual fear learning. Methods: Rats received 0 or 15 footshocks on postnatal day 17, an established model of acute ELS (aELS) that yields enhanced adult fear learning. In adulthood, rats received bilateral infusions of a vehicle, a 5-HT2C receptor antagonist (RS-102221), or a 5-HT2C receptor agonist (MK-212) into the BNST 15 min prior to one-footshock contextual fear conditioning in a novel context. The next day, rats were returned to the fear-conditioning context to assess their fear memory (freezing). Results: Females demonstrated aELS-induced enhancement in contextual fear learning, while males did not. BNST infusions of RS-102221 reduced contextual fear conditioning, independent of aELS condition and sex. Infusions of MK-212 had no effect. Conclusions: Taken together, these data suggest that serotonergic signaling through 5-HT2C receptors in the BNST contributes to contextual fear conditioning, but not aELS-induced stress-enhanced fear learning (SEFL).<\/jats:p>","DOI":"10.3390\/brainsci14121287","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T02:39:56Z","timestamp":1734921596000},"page":"1287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["5-HT2C Receptors in the BNST Modulate Contextual Fear Conditioning Without Affecting Acute Early Life Stress-Enhanced Fear Learning in Adult Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Brianna L.","family":"Minshall","sequence":"first","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5327-728X","authenticated-orcid":false,"given":"Catherine F.","family":"Wasylyshyn","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate M.","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Bartoszek","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennedy A.","family":"Seipel","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline M.","family":"Booms","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy C.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda N.","family":"Reichert","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob R.","family":"Dowell","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles L.","family":"Buck","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9830-4187","authenticated-orcid":false,"given":"Henry T.","family":"Beckett","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-5575","authenticated-orcid":false,"given":"Christopher A.","family":"Lowry","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). 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