{"doi":"10.1101/2023.09.25.559347","title":"A suite of engineered mice for interrogating psychedelic drug actions","abstract":"ABSTRACT 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 Htr2a -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 Htr2a mouse line and an additional constitutive Htr2A -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 in vivo .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390017,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9415,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1161847,"name":"Ariel Y. Deutch","orcid":null,"position":1,"is_corresponding":false},{"id":908146,"name":"Wei Wang","orcid":"0000-0002-4628-1755","position":2,"is_corresponding":false},{"id":549042,"name":"Gavin P. Schmitz","orcid":null,"position":3,"is_corresponding":false},{"id":998025,"name":"Karen Huang","orcid":null,"position":4,"is_corresponding":false},{"id":804232,"name":"D. Dewran Koçak","orcid":"0000-0001-6934-6964","position":5,"is_corresponding":false},{"id":1161257,"name":"Pierre Llorach","orcid":"0000-0002-4457-7800","position":6,"is_corresponding":false},{"id":1161848,"name":"Kasey Bowyer","orcid":null,"position":7,"is_corresponding":false},{"id":237735,"name":"Bei Liu","orcid":"0000-0001-5979-3082","position":8,"is_corresponding":false},{"id":265249,"name":"Noah Sciaky","orcid":null,"position":9,"is_corresponding":false},{"id":436873,"name":"Kunjie Hua","orcid":null,"position":10,"is_corresponding":false},{"id":390354,"name":"Chongguang Chen","orcid":"0000-0003-3097-8176","position":11,"is_corresponding":false},{"id":1106450,"name":"Sarah E. Mott","orcid":null,"position":12,"is_corresponding":false},{"id":337827,"name":"Jesse K. Niehaus","orcid":"0000-0002-6800-4134","position":13,"is_corresponding":false},{"id":225467,"name":"Jeffrey F. DiBerto","orcid":"0000-0002-8227-2071","position":14,"is_corresponding":false},{"id":225468,"name":"Justin G. 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Roth","orcid":"0000-0002-0561-6520","position":21,"is_corresponding":false},{"id":391558,"name":"Yi-Ting Chiu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":115,"raw_metadata":null,"created_at":"2026-07-19T01:18:32.854511Z","pmid":"37808655","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}