{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:26:12Z","timestamp":1789007172131,"version":"build-2803163510"},"reference-count":69,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Fear\u2010related psychiatric disorders such as phobias and anxiety are insufficiently treated by current therapies. Psychedelics targeting 5\u2010HT\u2082\n                      <jats:sub>A<\/jats:sub>\n                      receptors show promise in modulating fear circuits, but their specific neurobiological substrates remain unclear. This study investigates the effects of 4\u2010acetoxy\u2010\n                      <jats:italic>N<\/jats:italic>\n                      ,\n                      <jats:italic>N<\/jats:italic>\n                      \u2010dimethyltryptamine (4\u2010AcO\u2010DMT), a psychedelic compound, on innate fear responses and elucidates its underlying cortical microcircuits, focusing on predator odour\u2010evoked 22\u2010kHz ultrasonic vocalizations (USVs) in rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Using an optimized paradigm of 2,4,5\u2010trimethylthiazoline (TMT)\u2010induced 22\u2010kHz USVs in rats, the effects of 4\u2010AcO\u2010DMT were evaluated, and the dose\u2013response relationships were investigated. In behavioural experiments, we demonstrated that 4\u2010AcO\u2010DMT suppresses 22\u2010kHz USVs by reducing fear\u2010related response in rats. Brain\u2010wide EGR1 expression and targeted brain region lesions were employed to identify the brain region through which 4\u2010AcO\u2010DMT acts. Specific neuronal ablation and chemogenetic manipulation were applied to determine the types of neurons modulated by 4\u2010AcO\u2010DMT, and receptor antagonism and localized receptor knockout strategies were used to identify the receptor subtypes involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      4\u2010AcO\u2010DMT significantly suppressed TMT evoked 22\u2010kHz USVs via 5\u2010HT\u2082\n                      <jats:sub>A<\/jats:sub>\n                      receptor activation. This fear attenuation was mediated by recruitment of VIP interneurons in the prelimbic cortex (PrL), as chemogenetic activation of these cells abolished the behavioural effect. A cortical microcircuit mechanism\u20145\u2010HT\u2082\n                      <jats:sub>A<\/jats:sub>\n                      receptor\u2010driven vasoactive intestinal polypeptide (VIP) interneuron engagement\u2014is critical to 4\u2010AcO\u2010DMT \u2010induced suppression of innate fear responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      Our study reveals that 5\u2010HT\u2082\n                      <jats:sub>A<\/jats:sub>\n                      receptor activation by 4\u2010AcO\u2010DMT suppresses innate fear through VIP interneuron\u2010mediated modulation in the prelimbic cortex, advancing the neurobiological understanding of serotonergic psychedelics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LINKED ARTICLES<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.14\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.14\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70307","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:33:02Z","timestamp":1773001982000},"page":"4072-4088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["5\u2010HT\n                    <sub>2A<\/sub>\n                    receptors in the prelimbic cortex VIP\u2010expressing interneurons: A mechanism for psychedelic\u2010induced innate fear attenuation"],"prefix":"10.1111","volume":"183","author":[{"given":"Yuanyuan","family":"Wang","sequence":"first","affiliation":[{"name":"State Key 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