{"doi":"10.5937/medi0-57913","title":"Prolonged blockade of NMDA receptors and positive modulation of a5 GABA A receptors: No changes in depressive-like behavior, while the former slightly increased emotional reactivity in unstressed rats","abstract":"Introduction: Depression is a multifaceted disorder with a limited therapeutic repertoire. A significant breakthrough in depression research has been the discovery of fast-acting antidepressants that target the glutamate/GABA system, namely ketamine and neurosteroids. Positive modulation of GABA A receptors containing the a5 subunit (a5GABAARs) represents a promising new approach for targeted therapy of depression. The aim of this study was to investigate the effects of repeated administration of ketamine, an NMDA antagonist, and GL-II-73, a positive allosteric modulator at a5GABAARs, on behavioral despair, anxiety, and locomotor activity. Material and Methods: The experiments were performed on adult male Sprague-Dawley rats. Animals were treated for 7 days with either 6 mg/kg or 10 mg/kg ketamine in an intermittent dosing regimen, 10 mg/kg GL-II-73, or solvent. Following treatment, we performed a battery of behavioral tests consisting of forced swim test (FST), spontaneous locomotor activity (SLA), and novelty suppressed feeding test (NSFT). Results: No change was detected in any of the treatment groups regarding performance in the FST and NSFT. In SLA, all forms of treatment caused a decrease in the percentage of central time at both 10 and 30 minutes. Central distance was reduced at 10 and 30 minutes only after the 10 mg/kg dose of ketamine. Conclusion: Ketamine at the higher dose (10 mg/kg) elicited behavioral changes consistent with a slight increase in emotional reactivity, while minor changes of the same quality in the lower-dose ketamine and GL-II-73 groups hardly reflect any anxiety-inducing influence.","journal":"Medicinska istrazivanja","year":2025,"id":573310,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"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":1387520,"name":"Jana Ivanović","orcid":"0009-0003-1674-9956","position":1,"is_corresponding":false},{"id":1387515,"name":"Kristina Jezdić","orcid":"0009-0000-2208-2252","position":2,"is_corresponding":false},{"id":524992,"name":"Dishary Sharmin","orcid":"0000-0003-0417-4262","position":3,"is_corresponding":false},{"id":765734,"name":"Jovana Aranđelović","orcid":"0000-0002-0837-7027","position":4,"is_corresponding":false},{"id":445008,"name":"James M. Cook","orcid":"0000-0001-5512-3022","position":5,"is_corresponding":false},{"id":454644,"name":"Miroslav M. Savić","orcid":"0000-0002-6934-9193","position":6,"is_corresponding":false},{"id":1081841,"name":"Djordje Djorović","orcid":"0000-0003-0984-1343","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:57:32.445190Z","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":[]}