{"doi":"10.1124/jpet.116.239228","title":"Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine","abstract":null,"journal":"The Journal of Pharmacology and Experimental Therapeutics","year":2017,"id":673762,"datarank":0.8300084233091282,"base_score":5.53338948872752,"endowment":5.53338948872752,"self_citation_contribution":0.8300084233091282,"citation_network_contribution":0.0,"self_endowment_contribution":0.8300084233091282,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":252,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1760349,"name":"Hidetoh Toki","orcid":null,"position":1,"is_corresponding":false},{"id":1760351,"name":"Michihiko Iijima","orcid":null,"position":2,"is_corresponding":false},{"id":1760354,"name":"Takashi Hashihayata","orcid":null,"position":3,"is_corresponding":false},{"id":1760356,"name":"Jun-ichi Yamaguchi","orcid":null,"position":4,"is_corresponding":false},{"id":477825,"name":"Kenji Hashimoto","orcid":"0000-0002-8892-0439","position":5,"is_corresponding":false},{"id":1581379,"name":"Shigeyuki Chaki","orcid":null,"position":6,"is_corresponding":false},{"id":1760347,"name":"Kenichi Fukumoto","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine","abstract":"The rapid-acting and long-lasting antidepressant effects of (<i>R,S</i>)-ketamine have recently gained much attention. Although (<i>S</i>)-ketamine has been studied as an active isomer, recent evidence suggests that (<i>R</i>)-ketamine exhibits longer-lasting antidepressant effects than (<i>S</i>)-ketamine in rodents. However, the antidepressant potential of (<i>R</i>)-ketamine has not been fully addressed. In the present study, we compared the antidepressant effects of (<i>R</i>)-ketamine with those of (<i>S</i>)-ketamine in animal models of depression, including a model that is refractory to current medications. Both (<i>R</i>)-ketamine and (<i>S</i>)-ketamine exhibited antidepressant effects at 30 minutes as well as at 24 hours after administration in forced-swimming and tail-suspension tests in mice. At 48 hours after administration, however, (<i>R</i>)-ketamine still exerted a significant antidepressant effect in the tail-suspension test, whereas the effect of (<i>S</i>)-ketamine was no longer observed. Moreover, (<i>R</i>)-ketamine, but not (<i>S</i>)-ketamine, significantly reversed the depressive-like behavior induced by repeated treatments with corticosterone in rats at 24 hours after a single administration. This effect was attenuated by an <i>α</i>-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, suggesting the involvement of AMPA receptor stimulation in the effects. Both (<i>R</i>)-ketamine and (<i>S</i>)-ketamine exhibited practically the same exposure levels in plasma, brain, and cerebrospinal fluid in mice and rats, and both compounds were rapidly eliminated from plasma (<4-8 hours). The present results confirmed the previous findings that (<i>R</i>)-ketamine exerted longer-lasting antidepressant effects than (<i>S</i>)-ketamine in animal models of depression. Moreover, our study is the first to demonstrate that (<i>R</i>)-ketamine exerted a sustained antidepressant effect even in a model that is refractory to currently prescribed antidepressants.","is_dataset_classified":null,"base_score":5.53338948872752,"endowment":5.53338948872752,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28115553","pmcid":null,"openalex_id":"https://openalex.org/W2581419519","authors":[],"funders":[],"total_grants":0,"fwci":20.1128,"citation_percentile":0.99730724,"influential_citations":0,"citation_trend":[{"year":2017,"count":19},{"year":2018,"count":24},{"year":2019,"count":26},{"year":2020,"count":37},{"year":2021,"count":35},{"year":2022,"count":33},{"year":2023,"count":25},{"year":2024,"count":29},{"year":2025,"count":17},{"year":2026,"count":7}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0022356524195390?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022356524195390?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1124/jpet.116.239228","host_type":"publisher"},{"url":"https://doi.org/10.1124/jpet.116.239228","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28115553","host_type":"repository"}],"fields_of_study":["Treatment of Major Depression","Tryptophan and brain disorders","Neuroscience and Neuropharmacology Research","Animals","Antidepressive Agents","Depression","Dose-Response Relationship, Drug","Hindlimb Suspension","Ketamine","Locomotion","Male","Mice","Mice, Inbred C57BL","Mice, Inbred ICR","Rats","Rats, Sprague-Dawley","Stereoisomerism","Swimming"],"mesh_terms":["Animals","Antidepressive Agents","Depression","Dose-Response Relationship, Drug","Ketamine","Locomotion","Male","Mice, Inbred C57BL","Mice, Inbred ICR","Stereoisomerism","Swimming","Rats, Sprague-Dawley","Hindlimb Suspension","Mice","Rats"],"keywords":["Ketamine","Antidepressant","Tail suspension test","NMDA receptor","Pharmacology","Animal models of depression","Antagonist","Behavioural despair test","AMPA receptor","Medicine","Anesthesia","Internal medicine","Hippocampus","Receptor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T14:25:25.817742Z","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":[]}