{"doi":"10.1126/science.adf0435","title":"Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors","abstract":"Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex.","journal":"Science","year":2023,"id":314743,"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":468,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":227730,"name":"Lee E. Dunlap","orcid":"0000-0002-9365-8025","position":1,"is_corresponding":false},{"id":249810,"name":"Chunyang Dong","orcid":"0000-0002-4820-4454","position":2,"is_corresponding":false},{"id":1014004,"name":"Samuel J. Carter","orcid":"0000-0002-2276-4373","position":3,"is_corresponding":false},{"id":227718,"name":"Robert J. Tombari","orcid":"0000-0002-6561-8181","position":4,"is_corresponding":false},{"id":1014005,"name":"Shekib A. Jami","orcid":"0000-0001-5478-1963","position":5,"is_corresponding":false},{"id":227717,"name":"Lindsay P. Cameron","orcid":"0000-0002-8420-7898","position":6,"is_corresponding":false},{"id":785719,"name":"Seona D. Patel","orcid":"0000-0001-8947-4533","position":7,"is_corresponding":false},{"id":1014006,"name":"Joseph J. Hennessey","orcid":"0000-0003-0981-4695","position":8,"is_corresponding":false},{"id":492346,"name":"Hannah N. Saeger","orcid":"0000-0002-3055-5547","position":9,"is_corresponding":false},{"id":225472,"name":"John D. McCorvy","orcid":"0000-0001-7555-9413","position":10,"is_corresponding":false},{"id":497917,"name":"J.A. Gray","orcid":"0000-0002-7287-0748","position":11,"is_corresponding":false},{"id":249828,"name":"Lin Tian","orcid":"0000-0001-7012-6926","position":12,"is_corresponding":false},{"id":227738,"name":"David E. Olson","orcid":"0000-0002-4517-0543","position":13,"is_corresponding":false},{"id":227722,"name":"Maxemiliano V. Vargas","orcid":"0000-0002-3637-1896","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:06:02.898877Z","pmid":"36795823","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":[]}