{"doi":"10.1101/2025.05.29.656898","title":"Slow-Timescale Regulation of Dopamine Release and Mating Drive Over Days","abstract":"The rise and fall of motivational states may take place over timescales as long as many days. We used mouse mating behavior to model how the brain orchestrates slow-timescale changes in motivation. Male mice become sexually satiated after successful matings, and their motivation to mate gradually recovers over a week. Using deep-brain fluorescence-lifetime imaging in the medial preoptic area (MPOA), we found that tonic dopamine transmission-which regulates mating drive-also declined after mating and re-emerged over a week. Two mechanisms regulated dopamine transmission. First, successful mating transiently reduced tonic firing of hypothalamic dopamine-releasing neurons, thereby inhibiting dopamine release and mating behavior. Second, mating reduced the ability of these neurons to produce and release dopamine, and this ability gradually returned over the week-long recovery time course. Therefore, fast and slow mechanisms of neuronal plasticity cooperate to control the early and late phases of motivational dynamics, respectively.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":567377,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":243929,"name":"Joseph C. Madara","orcid":null,"position":1,"is_corresponding":false},{"id":1210384,"name":"Lauren F. Christenson","orcid":null,"position":2,"is_corresponding":false},{"id":631333,"name":"A M Díaz","orcid":null,"position":3,"is_corresponding":false},{"id":1471761,"name":"J. Y. Chen","orcid":null,"position":4,"is_corresponding":false},{"id":374424,"name":"Luca Ravotto","orcid":"0000-0002-0431-9866","position":5,"is_corresponding":false},{"id":250394,"name":"Tommaso Patriarchi","orcid":"0000-0001-9351-3734","position":6,"is_corresponding":false},{"id":241947,"name":"Mark L. Andermann","orcid":"0000-0002-9882-933X","position":7,"is_corresponding":false},{"id":630126,"name":"Stephen X. Zhang","orcid":"0000-0001-7743-9247","position":8,"is_corresponding":false},{"id":1210385,"name":"Praneel S. Sunkavalli","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:56:44.340853Z","pmid":"40501937","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":[]}