{"doi":"10.1002/brb3.70616","title":"Differential Modulation of Glutamate Transporter‐1 by Cocaine and Oxycodone and the Efficacy of MC‐100093 to Reduce Reinstatement of Self‐Administration","abstract":"INTRODUCTION: Despite the widespread impact of opioid use disorder, pharmacological options for treatment remain limited. Recent studies find that cocaine exposure decreases the expression of the glutamate transporter GLT-1 in the nucleus accumbens (NAc) and that treatment with the beta-lactam antibiotic ceftriaxone rescues this loss of expression and reduces cue-induced reinstatement to cocaine self-administration. The novel beta-lactam derivative MC-100093 (093) lacks antimicrobial properties but crosses the blood-brain barrier more rapidly and retains the beneficial effects of ceftriaxone following cocaine. However, 093 effects following oxycodone exposure have not been examined. METHODS: We used intravenous self-administration (IVSA) of oxycodone in rats to test if 093 can attenuate oxycodone seeking. Membrane expression of GLT-1 in the NAc was investigated using western blots. Conditioned place preference (CPP) was used to test the effect of oxycodone and cocaine alone on GLT-1 expression. RESULTS: We find that 093 injections following IVSA of oxycodone in rats did not reduce cue-induced reinstatement. Interestingly, western blot analysis revealed that 093 failed to upregulate the expression of GLT-1 in the NAc of oxycodone-exposed animals. Follow-up CPP experiments suggest that oxycodone exposure alone does not decrease GLT-1 expression as cocaine does. CONCLUSIONS: Our results indicate that drug-specific reductions in NAc GLT-1 expression may be necessary for 093's efficacy. Further investigation into 093 and other opioids is needed to fully understand their relationship with GLT-1 expression and beta-lactams.","journal":"Brain and Behavior","year":2025,"id":536362,"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":0.9554,"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":684807,"name":"Yanaira Alonso‐Caraballo","orcid":"0000-0002-7553-4408","position":1,"is_corresponding":false},{"id":1421683,"name":"Britta Hornback","orcid":null,"position":2,"is_corresponding":false},{"id":1421684,"name":"Angel Robert","orcid":null,"position":3,"is_corresponding":false},{"id":1421180,"name":"Megan A. Brickner","orcid":"0000-0002-3020-718X","position":4,"is_corresponding":false},{"id":1377007,"name":"Manuel Esguerra","orcid":"0000-0002-6934-5424","position":5,"is_corresponding":false},{"id":721033,"name":"Wayne E. Childers","orcid":"0000-0003-0527-3684","position":6,"is_corresponding":false},{"id":721034,"name":"Magid Abou‐Gharbia","orcid":"0000-0001-7524-6011","position":7,"is_corresponding":false},{"id":232008,"name":"Mark J. Thomas","orcid":"0000-0001-5721-5350","position":8,"is_corresponding":false},{"id":816674,"name":"Damyan W. Hart","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:52:05.227140Z","pmid":"40635497","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":[]}