{"doi":"10.1016/j.biopsych.2025.03.024","title":"Noradrenaline Modulates Central Amygdala GABA Transmission and Alcohol Drinking in Female Rats","abstract":"Background Alcohol use disorder (AUD) is a chronic relapsing disorder and a leading preventable cause of death worldwide. The central nucleus of the amygdala (CeA) is a hub for stress and AUD. Norepinephrine (NE), also known as noradrenaline, regulates the brain's response to stress and alcohol. We previously reported that α 1 -adrenergic receptors drive moderate alcohol intake, while β receptors contribute to excessive drinking associated with dependence in male rats. Methods Here, we determined that alcohol dependence and withdrawal alter the CeA noradrenergic system in female rats using ex vivo electrophysiology, in situ hybridization, and site-specific behavioral pharmacology. We also analyzed RNA-sequencing data from postmortem CeA samples obtained from female donors with and without AUD. Results NE bidirectionally (increase and decrease) modulated CeA GABAergic (gamma-aminobutyric acidergic) transmission via both α 1 and β receptors. Prazosin, an α 1 receptor antagonist, reduced moderate alcohol intake in nondependent female rats and excessive drinking in dependent females, while propranolol, a β receptor antagonist, reduced excessive drinking only in dependent females. While withdrawal produced a partial functional recovery of NE modulation of the CeA, some of the cellular patterns of adrenergic receptor messenger RNA expression persisted. Although we did not observe any differences in adrenergic receptor gene expression in the CeA from our human AUD donors, we found a downregulation of ADRA1A in the basolateral amygdala and the dorsolateral prefrontal cortex compared with control donors. Conclusions Amygdalar α 1 - and β-adrenergic receptors are key neural substrates of AUD. Our results support ongoing development of receptor-specific medication for AUD and highlight promising efficacy in females.","journal":"Biological Psychiatry","year":2025,"id":516576,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9637,"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":1246091,"name":"Chloe M. Erikson","orcid":"0009-0007-1993-1752","position":1,"is_corresponding":false},{"id":264358,"name":"Francisco J. Flores‐Ramirez","orcid":"0000-0002-5839-3332","position":2,"is_corresponding":false},{"id":449733,"name":"Larry Rodriguez","orcid":"0000-0002-9591-5005","position":3,"is_corresponding":false},{"id":971217,"name":"Riccardo Barchiesi","orcid":"0000-0002-0514-2628","position":4,"is_corresponding":false},{"id":748746,"name":"Valentina Vozella","orcid":"0000-0001-6868-3424","position":5,"is_corresponding":false},{"id":874799,"name":"Vittoria Borgonetti","orcid":"0000-0002-2203-5285","position":6,"is_corresponding":false},{"id":473538,"name":"Bryan Cruz","orcid":"0000-0002-7418-1524","position":7,"is_corresponding":false},{"id":724182,"name":"Cristina Zalfa","orcid":"0000-0001-8472-1961","position":8,"is_corresponding":false},{"id":720453,"name":"Kiley Hughes","orcid":"0000-0002-8005-8565","position":9,"is_corresponding":false},{"id":473071,"name":"Pauravi J. Gandhi","orcid":"0000-0002-9793-9107","position":10,"is_corresponding":false},{"id":262439,"name":"Michal Bajo","orcid":"0000-0003-1102-2689","position":11,"is_corresponding":false},{"id":262441,"name":"Roman Vlkolinský","orcid":"0000-0002-9786-0407","position":12,"is_corresponding":false},{"id":262443,"name":"R. Dayne Mayfield","orcid":"0000-0002-8045-1789","position":13,"is_corresponding":false},{"id":723166,"name":"Rémi Martin‐Fardon","orcid":"0000-0002-7470-5885","position":14,"is_corresponding":false},{"id":262444,"name":"Marisa Roberto","orcid":"0000-0003-0729-3961","position":15,"is_corresponding":false},{"id":889414,"name":"Alexia Anjos-Santos","orcid":"0000-0001-7431-7148","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:48:49.486328Z","pmid":"40194754","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":[]}