{"doi":"10.1016/j.celrep.2023.113187","title":"Early-life stress and ovarian hormones alter transcriptional regulation in the nucleus accumbens resulting in sex-specific responses to cocaine","abstract":"Early-life stress and ovarian hormones contribute to increased female vulnerability to cocaine addiction. Here, we reveal molecular substrates in the reward area, the nucleus accumbens, through which these female-specific factors affect immediate and conditioning responses to cocaine. We find shared involvement of X chromosome inactivation-related and estrogen signaling-related gene regulation in enhanced conditioning responses following early-life stress and during the low-estrogenic state in females. Low-estrogenic females respond to acute cocaine by opening neuronal chromatin enriched for the sites of ΔFosB, a transcription factor implicated in chronic cocaine response and addiction. Conversely, high-estrogenic females respond to cocaine by preferential chromatin closing, providing a mechanism for limiting cocaine-driven chromatin and synaptic plasticity. We find that physiological estrogen withdrawal, early-life stress, and absence of one X chromosome all nullify the protective effect of a high-estrogenic state on cocaine conditioning in females. Our findings offer a molecular framework to enable understanding of sex-specific neuronal mechanisms underlying cocaine use disorder.","journal":"Cell Reports","year":2023,"id":343343,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"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":746357,"name":"Ivana Jarić","orcid":"0000-0002-8818-2974","position":1,"is_corresponding":false},{"id":1080875,"name":"Fabio Bellia","orcid":"0000-0002-8443-6084","position":2,"is_corresponding":false},{"id":675639,"name":"Heining Cham","orcid":"0000-0002-2933-056X","position":3,"is_corresponding":false},{"id":275114,"name":"John M. Greally","orcid":"0000-0001-6069-7960","position":4,"is_corresponding":false},{"id":585984,"name":"Masako Suzuki","orcid":"0000-0003-0605-9225","position":5,"is_corresponding":false},{"id":27844,"name":"Marija Kundaković","orcid":"0000-0002-6734-4217","position":6,"is_corresponding":false},{"id":746356,"name":"Devin Rocks","orcid":"0000-0002-3192-0219","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":null,"created_at":"2026-07-19T01:11:21.758449Z","pmid":"37777968","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":[]}