{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:44:58Z","timestamp":1793378698566,"version":"4.5.0"},"posted":{"date-parts":[[2023,9,26]]},"group-title":"Neuroscience","reference-count":136,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide a suite of engineered mice useful for clarifying the role of HTR2A and HTR2A-expressing neurons in psychedelic drug actions. We first generated\n                  <jats:italic>Htr2a<\/jats:italic>\n                  -EGFP-CT-IRES-CreERT2 mice (CT:C-terminus) to independently identify both HTR2A-EGFP-CT receptors and HTR2A-containing cells thereby providing a detailed anatomical map of HTR2A and identifying cell types that express HTR2A. We also generated a humanized\n                  <jats:italic>Htr2a<\/jats:italic>\n                  mouse line and an additional constitutive\n                  <jats:italic>Htr2A<\/jats:italic>\n                  -Cre mouse line. Psychedelics induced a variety of known behavioral changes in our mice validating their utility for behavioral studies. Finally, electrophysiology studies revealed that extracellular 5-HT elicited a HTR2A-mediated robust increase in firing of genetically-identified pyramidal neurons--consistent with a plasma membrane localization and mode of action. These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugs\n                  <jats:italic>in vivo<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2023.09.25.559347","type":"posted-content","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T16:55:13Z","timestamp":1695747313000},"source":"Crossref","is-referenced-by-count":17,"title":["A suite of engineered mice for interrogating psychedelic drug actions"],"prefix":"10.64898","author":[{"given":"Yi-Ting","family":"Chiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel Y.","family":"Deutch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin P","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Lu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Dewran","family":"Kocak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Llorach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasey","family":"Bowyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Sciaky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunjie","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongguang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Mott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Niehaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey F.","family":"DiBerto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9gory","family":"Scherrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A","family":"Herman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuhao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C","family":"Wetsel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023092907250631000_2023.09.25.559347v1.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1090-09.2009"},{"key":"2023092907250631000_2023.09.25.559347v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700293104"},{"key":"2023092907250631000_2023.09.25.559347v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(97)00102-7"},{"key":"2023092907250631000_2023.09.25.559347v1.4","doi-asserted-by":"publisher","DOI":"10.1124\/pr.118.015552"},{"key":"2023092907250631000_2023.09.25.559347v1.5","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.med.60.042307.110802","article-title":"The Expanded Biology of Serotonin","volume":"60","year":"2009","journal-title":"Annl Revf Med"},{"key":"2023092907250631000_2023.09.25.559347v1.6","first-page":"110","article-title":"Agonist-induced internalization of the 5HT(2A) receptor in vitro","volume":"39","year":"1996","journal-title":"Biol Psychiaty"},{"key":"2023092907250631000_2023.09.25.559347v1.7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404673200"},{"key":"2023092907250631000_2023.09.25.559347v1.8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006968200"},{"key":"2023092907250631000_2023.09.25.559347v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nn1525"},{"key":"2023092907250631000_2023.09.25.559347v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2396(20010315)39:4<297::AID-SYN1012>3.0.CO;2-Q"},{"key":"2023092907250631000_2023.09.25.559347v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(88)90342-6"},{"key":"2023092907250631000_2023.09.25.559347v1.12","first-page":"137","article-title":"Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain","volume":"3","year":"1990","journal-title":"Neuropsychopharmacology"},{"key":"2023092907250631000_2023.09.25.559347v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(92)90005-V"},{"key":"2023092907250631000_2023.09.25.559347v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990628)409:2<187::AID-CNE2>3.0.CO;2-P"},{"key":"2023092907250631000_2023.09.25.559347v1.15","unstructured":"Crawley, J.N . 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