{"doi":"10.31234/osf.io/b84zx","title":"Individual variability and sexually dimorphic fear memory-related effects of anxiety on fear extinction in inbred mouse model","abstract":"The ability to efficiently extinguish memory of a fearful event is critical for individual wellbeing. Fear extinction impairments are commonly observed in a variety of neuropsychiatric conditions, including anxiety disorders and PTSD. While inter-individual as well as sex-related differences in extinction are recognized, their biological underpinnings remain unclear. To examine neurobehavioral features that may contribute to extinction efficacy in genetically similar subjects, fear extinction was analyzed in cohorts of inbred wild-type male and female mice. While the overall efficacy rate of extinction was similar in both sexes, we observed a high level of inter-individual variation. We also found that anxiety phenotype and extinction efficacy were significantly linked, although this effect differed between male and female animals: high-anxiety male, but not female, mice tended to have lower extinction efficacy. Moreover, this link was observed only in male animals exhibiting strong memory of a fearful event. Finally, we discovered that male (but not female) mice showing high levels of extinction efficacy displayed significantly greater hippocampal expression of anxiety-related Corticotropin Releasing Hormone Receptor 2 (CRHR2) than their low extinction efficacy counterparts. These findings suggest the potentially important role of CRHR2 signaling in mediating sexually dimorphic effects of anxiety on fear extinction. The implications of our study are tied to the biological bases for fear-related disorders, such as PTSD, in human patients.","journal":"PsyArXiv (OSF Preprints)","year":2023,"id":400531,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"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":1177001,"name":"A.A. Rudenko","orcid":"0000-0001-9160-7315","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","pmid":null,"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":[]}