{"doi":"10.3389/fphar.2022.930346","title":"Altered Serotonin 2A (5-HT2A) Receptor Signaling Underlies Mild TBI-Elicited Deficits in Social Dominance","abstract":"Various forms of traumatic brain injury (TBI) are a leading cause of disability in the United States, with the generation of neuropsychiatric complications such as depression, anxiety, social dysfunction, and suicidality being common comorbidities. Serotonin (5-HT) signaling is linked to psychiatric disorders; however, the effects of neurotrauma on normal, homeostatic 5-HT signaling within the central nervous system (CNS) have not been well characterized. We hypothesize that TBI alters specific components of 5-HT signaling within the CNS and that the elucidation of specific TBI-induced alterations in 5-HT signaling may identify novel targets for pharmacotherapies that ameliorate the neuropsychiatric complications of TBI. Herein, we provide evidence that closed-head blast-induced mild TBI (mTBI) results in selective alterations in cortical 5-HT 2A receptor signaling. We find that mTBI increases in vivo cortical 5-HT 2A receptor sensitivity and ex vivo radioligand binding at time points corresponding with mTBI-induced deficits in social behavior. In contrast, in vivo characterizations of 5-HT 1A receptor function revealed no effect of mTBI. Notably, we find that repeated pharmacologic activation of 5-HT 2A receptors post-injury reverses deficits in social dominance resulting from mTBI. Cumulatively, these studies provide evidence that mTBI drives alterations in cortical 5-HT 2A receptor function and that selective targeting of TBI-elicited alterations in 5-HT 2A receptor signaling may represent a promising avenue for the development of pharmacotherapies for TBI-induced generation of neuropsychiatric disorders.","journal":"Frontiers in Pharmacology","year":2022,"id":271910,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":938458,"name":"Christopher O’Connell","orcid":null,"position":1,"is_corresponding":false},{"id":937753,"name":"Evan L. Reeder","orcid":"0000-0003-3119-4576","position":2,"is_corresponding":false},{"id":938459,"name":"Sophia V. Norman","orcid":null,"position":3,"is_corresponding":false},{"id":938460,"name":"Kainat Lungani","orcid":null,"position":4,"is_corresponding":false},{"id":938461,"name":"Poornima Gopalan","orcid":null,"position":5,"is_corresponding":false},{"id":653089,"name":"Gary A. Gudelsky","orcid":"0000-0003-2552-8592","position":6,"is_corresponding":false},{"id":491594,"name":"Matthew J. Robson","orcid":"0000-0002-3277-3062","position":7,"is_corresponding":false},{"id":938457,"name":"Sean M. Collins","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:27:43.806977Z","pmid":"35910378","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":[]}