The Involvement of the Serotonergic System in Ketamine and Fluoxetine Combination-induced Cognitive Impairments in Mice

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dc.contributor.authorUyar, Emre
dc.contributor.authorErdinc, Meral
dc.contributor.authorKelle, Lker
dc.contributor.authorErdinc, Levent
dc.contributor.authorSeker, Ugur
dc.contributor.authorNergiz, Yusuf
dc.date.accessioned2025-02-22T14:08:37Z
dc.date.available2025-02-22T14:08:37Z
dc.date.issued2024
dc.departmentDicle Üniversitesien_US
dc.description.abstractBackground: Gluta mater gic N-methyl-D-aspartate (NMDA) receptors play vital roles in memory formation. Changes in the activity of these receptors influence memory processes. Ketamine is a noncompetitive NMDA receptor antagonist drug with promising mood-altering and pain-reducing effects ff ects in low doses. These effects ff ects are believed to be related to altered serotonergic transmission. Methods: The present study investigated the involvement of the serotonergic system in low-dose ketamine administrations' effects ff ects on memory acquisition, consolidation, and retrieval processes. Sixty-four male BALB/c mice were used in this experiment and separated into 8t groups. Mice were treated subchronically with a selective serotonin reuptake inhibitor, fluoxetine, and a serotonin depletion agent, p-chlorophenylalanine (pCPA). A serotonin antagonist, methiothepin, and ketamine were acutely administered 60 minutes before or after the behavioral tests. A passive avoidance (PA) test measured emotional memory acquisition, consolidation, and retrieval processes. Hippocampi malondialdehyde (MDA) levels were analyzed, and histopathological examinations were performed. Results: Ketamine alone did not significantly affect ff ect memory encoding processes in the PA test, while the ketamine-fluoxetine combination disrupted memory consolidation. Fluoxetine negatively affected ff ected the memory acquisition process, which was normalized during the consolidation and retrieval trials. Drug applications did not significantly alter hippocampal MDA levels. In all ketamine-applied groups, histopathologic alterations were evident. Conclusion: Low-dose ketamine administration induces neurodegeneration, and it also impairs memory functions when combined with fluoxetine, indicating increased serotonergic transmission may be involved in the memory-impairing and neurotoxic effects ff ects of ketamine.en_US
dc.description.sponsorshipDicle University [14TF126]en_US
dc.description.sponsorshipFunding: This study is supported by Dicle University (grant number: 14TF126) .en_US
dc.identifier.doi10.5152/eurasianjmed.2024.23219
dc.identifier.endpage107en_US
dc.identifier.issn1308-8742
dc.identifier.issue2en_US
dc.identifier.pmid39128082en_US
dc.identifier.scopus2-s2.0-85196744810en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage102en_US
dc.identifier.trdizinid1275994en_US
dc.identifier.urihttps://doi.org/10.5152/eurasianjmed.2024.23219
dc.identifier.urihttps://search.trdizin.gov.tr/tr/yayin/detay/1275994
dc.identifier.urihttps://hdl.handle.net/11468/29514
dc.identifier.volume56en_US
dc.identifier.wosWOS:001292915000005
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakTR-Dizin
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherAtaturk Univen_US
dc.relation.ispartofEurasian Journal of Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKA_WOS_20250222
dc.subjectKetamineen_US
dc.subjectserotonergic systemen_US
dc.subjectpassive avoidance testen_US
dc.subjectemotional memoryen_US
dc.subjectbrain morphologyen_US
dc.titleThe Involvement of the Serotonergic System in Ketamine and Fluoxetine Combination-induced Cognitive Impairments in Miceen_US
dc.typeArticleen_US

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