{"doi":"10.1038/s41598-025-11208-2","title":"Absence of sex differences in serotonergic control of orbitofrontal cortex neuronal activity","abstract":"Abstract The orbitofrontal cortex (OFC) is a brain region involved in cognitive processing, especially in tasks that require flexibility in decision-making. Serotonin (5-HT) plays a critical role in mediating OFC-dependent behavior, primarily through its actions at both 5-HT 1 and 5-HT 2 receptors. Through these receptors, 5-HT acts both pre- and postsynaptically at pyramidal (PyN) neurons and parvalbumin-containing interneurons (OFC PV ) to regulate their activity. In a previous study, we reported that the non-selective 5-HT 2 antagonist ketanserin inhibited 5-HT-induced membrane currents in OFC PV neurons from female and not male rats, suggesting the possibility that this results from sex-dependent differential 5-HT 2A and 5-HT 2C receptor expression. Here, we test this hypothesis using subtype-selective antagonists, and we find that 5-HT-mediated depolarization of OFC PV neurons occurs via activation of 5-HT 2A , and not 5-HT 2C receptors. Additionally, 5-HT 2A receptor antagonism was equally effective in OFC PV neurons from males and females, as was the 5-HT 2 agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI). These pharmacological data suggest that the sex-dependent effects of ketanserin do not result from differential expression of 5-HT 2 receptor subtypes in OFC PV neurons. In addition, 5-HT effects on OFC PyNs are similar in males and females. In light of recent reports of sex-dependent differences in prefrontal cortical function, our results are presented to inform and clarify actions of 5-HT on OFC circuitry.","journal":"Scientific Reports","year":2025,"id":526281,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":499473,"name":"Alexander F. Hoffman","orcid":"0000-0002-2676-0628","position":1,"is_corresponding":false},{"id":499474,"name":"Carl R. Lupica","orcid":"0000-0002-5375-3263","position":2,"is_corresponding":false},{"id":1402387,"name":"Kailin M Mooney","orcid":null,"position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:50:30.402772Z","pmid":"40676159","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":[]}