{"doi":"10.1016/j.jsps.2024.102108","title":"Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine","abstract":"Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-β) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-β mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.","journal":"Saudi Pharmaceutical Journal","year":2024,"id":444721,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1260659,"name":"Ghadeer M.S. Swiss","orcid":null,"position":1,"is_corresponding":false},{"id":1260660,"name":"Fatin A. Alrashedi","orcid":null,"position":2,"is_corresponding":false},{"id":1260661,"name":"Kholoud A. Baeshen","orcid":null,"position":3,"is_corresponding":false},{"id":1260662,"name":"Sultan A. Alshammari","orcid":null,"position":4,"is_corresponding":false},{"id":506203,"name":"Shakir D. AlSharari","orcid":"0000-0002-4263-3610","position":5,"is_corresponding":false},{"id":1080677,"name":"Nemat Ali","orcid":"0000-0001-6525-4202","position":6,"is_corresponding":false},{"id":1080676,"name":"Abdullah F. Alasmari","orcid":"0000-0001-7569-4287","position":7,"is_corresponding":false},{"id":1053989,"name":"Ali Alhoshani","orcid":"0000-0002-3450-283X","position":8,"is_corresponding":false},{"id":1260181,"name":"Alaa Alnoor Alameen","orcid":"0000-0002-4073-2375","position":9,"is_corresponding":false},{"id":721033,"name":"Wayne E. Childers","orcid":"0000-0003-0527-3684","position":10,"is_corresponding":false},{"id":721034,"name":"Magid Abou‐Gharbia","orcid":"0000-0001-7524-6011","position":11,"is_corresponding":false},{"id":398345,"name":"Fawaz Alasmari","orcid":"0000-0003-2382-5892","position":12,"is_corresponding":false},{"id":383172,"name":"Youssef Sari","orcid":"0000-0002-6761-9786","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T02:01:37.886033Z","pmid":"38868175","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":[]}