{"doi":"10.1016/j.bpsgos.2024.100310","title":"Carbon Dioxide Reactivity Differentially Predicts Fear Expression After Extinction and Retrieval-Extinction in Rats","abstract":"Cues present during a traumatic event may result in persistent fear responses. These responses can be attenuated through extinction learning, a core component of exposure therapy. Exposure/extinction is effective for some, but not all. We recently demonstrated that carbon dioxide (CO2) reactivity predicts fear extinction memory and orexin activation, and that orexin activation predicts fear extinction memory, suggesting that a CO2 challenge may enable identifying whether an individual is a good candidate for an extinction-based approach. Another method to attenuate conditioned responses, retrieval-extinction, renders the original associative memory labile via distinct neural mechanisms. The purpose of the present study was to examine whether we could replicate previous findings that retrieval-extinction is more effective than extinction at preventing the return of fear and that CO2 reactivity predicts fear memory after extinction. We also examined whether CO2 reactivity predicts fear memory after retrieval-extinction. Male rats first underwent a CO2 challenge and fear conditioning and were assigned to receive either standard extinction (n = 28) or retrieval-extinction (n = 28). They then underwent a long-term memory (LTM) test and a reinstatement test. We found that retrieval-extinction resulted in lower freezing during extinction, LTM, and reinstatement than standard extinction. Using the best subset approach to linear regression, we found that CO2 reactivity predicts LTM after extinction, and also predicts LTM after retrieval-extinction, albeit to a lesser degree. CO2 reactivity could be used as a screening tool to determine whether an individual might be a good candidate for an extinction-based therapeutic approach.","journal":"Biological Psychiatry Global Open Science","year":2024,"id":450054,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1095334,"name":"Nicole E. Keller","orcid":"0000-0002-0259-6720","position":1,"is_corresponding":false},{"id":1248692,"name":"Laura A. Agee","orcid":"0000-0002-1637-1901","position":2,"is_corresponding":false},{"id":708455,"name":"Jason Shumake","orcid":null,"position":3,"is_corresponding":false},{"id":443309,"name":"Jasper A. J. Smits","orcid":"0000-0003-1633-9693","position":4,"is_corresponding":false},{"id":410161,"name":"Michael J. Telch","orcid":"0000-0003-3444-8500","position":5,"is_corresponding":false},{"id":443307,"name":"Michael W. Otto","orcid":"0000-0002-8915-7578","position":6,"is_corresponding":false},{"id":1270641,"name":"Hongjoo J. Lee","orcid":null,"position":7,"is_corresponding":false},{"id":410160,"name":"Marie‐H. Monfils","orcid":"0000-0001-8971-6651","position":8,"is_corresponding":false},{"id":1270640,"name":"Marissa Raskin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:02:25.004119Z","pmid":"38680941","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":[]}