{"doi":"10.1126/sciadv.aaz1050","title":"Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala","abstract":"Behavioral and clinical studies suggest a critical role of substance P (SP)/neurokinin-1 receptor (NK-1R) signaling in alcohol dependence. Here, we examined regulation of GABA transmission in the medial subdivision of the central amygdala (CeM) by the SP/NK-1R system, and its neuroadaptation following chronic alcohol exposure. In naïve rats, SP increased action potential-dependent GABA release, and the selective NK-1R antagonist L822429 decreased it, demonstrating SP regulation of CeM activity under basal conditions. SP induced a larger GABA release in alcohol-dependent rats accompanied by decreased NK-1R expression compared to naïve controls, suggesting NK-1R hypersensitivity which persisted during protracted alcohol withdrawal. The NK-1R antagonist blocked acute alcohol-induced GABA release in alcohol-dependent and withdrawn but not in naïve rats, indicating that dependence engages the SP/NK-1R system to mediate acute effects of alcohol. Collectively, we report long-lasting CeA NK-1R hypersensitivity corroborating that NK-1Rs are promising targets for the treatment of alcohol use disorder.","journal":"Science Advances","year":2020,"id":99030,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":262509,"name":"Thomas Steinkellner","orcid":"0000-0003-4591-4992","position":1,"is_corresponding":false},{"id":262516,"name":"Thomas S. Hnasko","orcid":"0000-0001-6176-8513","position":2,"is_corresponding":false},{"id":262444,"name":"Marisa Roberto","orcid":"0000-0003-0729-3961","position":3,"is_corresponding":false},{"id":262436,"name":"Sophia Khom","orcid":"0000-0003-3567-8973","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T22:37:35.547042Z","pmid":"32206720","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":[]}