{"doi":"10.1101/2023.12.09.570945","title":"Estrogenic control of reward prediction errors and reinforcement learning","abstract":"Gonadal hormones act throughout the brain 1 , and neuropsychiatric disorders vary in symptom severity over the reproductive cycle, pregnancy, and perimenopause 2–4 . Yet how hormones influence cognitive processes is unclear. Exogenous 17 β -estradiol modulates dopamine signaling in the nucleus accumbens core (NAcc) 5,6 , which instantiates reward prediction errors (RPEs) for reinforcement learning 7–16 . Here we show that endogenous 17 β -estradiol enhances RPEs and sensitivity to previous rewards by reducing dopamine reuptake proteins in the NAcc. Rats performed a task with different reward states; they adjusted how quickly they initiated trials across states, balancing effort against expected rewards. NAcc dopamine reflected RPEs that predicted and causally influenced initiation times. Elevated endogenous 17 β -estradiol increased sensitivity to reward states by enhancing dopaminergic RPEs in the NAcc. Proteomics revealed reduced dopamine transporter expression. Finally, knockdown of midbrain estrogen receptors suppressed reinforcement learning. 17 β -estradiol therefore controls RPEs via dopamine reuptake, mechanistically revealing how hormones influence neural dynamics for motivation and learning.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391150,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":1163456,"name":"Audrey Martin","orcid":"0000-0003-3402-1339","position":1,"is_corresponding":false},{"id":1163909,"name":"Daljit Kaur","orcid":null,"position":2,"is_corresponding":false},{"id":1046307,"name":"Andrew Mah","orcid":"0000-0002-3425-2498","position":3,"is_corresponding":false},{"id":1163910,"name":"Diana H. Levy","orcid":null,"position":4,"is_corresponding":false},{"id":1028200,"name":"Takashi Yamaguchi","orcid":"0000-0001-5153-940X","position":5,"is_corresponding":false},{"id":699692,"name":"Amy W. Lasek","orcid":"0000-0002-7099-2442","position":6,"is_corresponding":false},{"id":226424,"name":"Dayu Lin","orcid":"0000-0003-2006-0791","position":7,"is_corresponding":false},{"id":374477,"name":"Chiye Aoki","orcid":"0000-0003-4010-9425","position":8,"is_corresponding":false},{"id":1046308,"name":"Christine M. Constantinople","orcid":"0000-0003-4435-4460","position":9,"is_corresponding":false},{"id":1018236,"name":"Carla E. M. Golden","orcid":"0000-0003-1445-3724","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":"38105956","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":[]}