{"doi":"10.1101/2020.08.31.276253","title":"Oxycodone self-administration activates the mitogen-activated protein kinase/mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum","abstract":"ABSTRACT To identify signaling pathways activated by oxycodone self-administration (SA), Sprague-Dawley rats self-administered oxycodone for 20 days using short-access (ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized two hours after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs in the LgA-H rats. GluA3 , but not GluA2 , expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. Our findings indicate that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation, which promoted increases in striatal gene expression. Our observations offer novel avenues for pharmacological interventions against oxycodone addiction.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":127907,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"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":34349,"name":"Michael T. McCoy","orcid":"0000-0001-7457-7660","position":1,"is_corresponding":false},{"id":34351,"name":"Bruce Ladenheim","orcid":"0000-0001-9124-6994","position":2,"is_corresponding":false},{"id":34352,"name":"Jean Lud Cadet","orcid":"0000-0001-5635-3524","position":3,"is_corresponding":false},{"id":442033,"name":"Christopher A. Blackwood","orcid":"0000-0002-9938-3843","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T23:15:34.966380Z","pmid":null,"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":[]}