Browsing by Author "Erdinc, Levent"

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The Involvement of the Serotonergic System in Ketamine and Fluoxetine Combination-Induced Cognitive Impairments in Mice
(Ataturk Univ, 2024) Şeker, Uğur; Erdinc, Meral; Kelle, Lker; Erdinc, Levent; Seker, Ugur; Nergiz, Yusuf; Department of Basic Medical Sciences / Temel Tıp Bilimleri Bölümü
Background: 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.
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Protective Effects of Trolox on Ketamine-Induced Memory Impairments and Morphological Changes in the Brain
(Asian Network Scientific Information-Ansinet, 2025) Şeker, Uğur; Erdinc, Meral; Kelle, Ilker; Erdinc, Levent; Seker, Ugur; Nergiz, Yusuf; Department of Basic Medical Sciences / Temel Tıp Bilimleri Bölümü
Background and Objective: Ketamine has demonstrated potential in treating various neuropsychiatric disorders at low doses. However, its memory-impairing and neurotoxic effects and abuse potential present limitations to its use. This study aimed to investigate ketamine's effects on memory functions, brain morphology and lipid peroxidation in a time- and dose-dependent manner and the protective effects of Trolox. Materials and Methods: Forty-eight male BALB/c mice were administered low and high doses of ketamine (10, 30 mg/kg/day, respectively) sub-chronically and chronically (7 and 21 days, respectively). A subgroup also received Trolox (20 mg/kg/day) for 21 days combined with high-dose ketamine. Following the drug administrations, behavioral tests were performed, including a modified elevated plus maze, a novel object recognition and a passive avoidance test. In the brain, malondialdehyde levels and morphology were examined. The results were analyzed using a one-way analysis of variance followed by a post hoc Tukey's test. Results: Chronic high-dose ketamine impaired spatial, emotional and recognition memory. Subchronic high-dose ketamine did not affect emotional and recognition memory but did impair spatial memory. Low-dose ketamine did not produce impairments. Malondialdehyde levels were elevated and morphological changes were evident in the chronic high-dose ketamine-applied group. These alterations were attenuated with Trolox. Conclusion: The memory-impairing and neurotoxic effects of ketamine are linked to increased oxidative stress. Antioxidant molecules like Trolox can be practical against the toxicity of ketamine.