Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic
Schizophrenia is a major neuropsychiatric disorder associated with neurochemical perturbations characterized by behavioral abnormalities, for which effective treatment remains elusive. The current study investigated the neurotransmitter modulatory effect of diosmin in preventing and reversing ketami...
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Elsevier
2025-06-01
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| Series: | Brain Disorders |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666459325000307 |
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| author | Aya-Ebi Okubo Eneni Benneth Ben-Azu Abayomi Mayowa Ajayi Adegbuyi Oladele Aderibibge |
| author_facet | Aya-Ebi Okubo Eneni Benneth Ben-Azu Abayomi Mayowa Ajayi Adegbuyi Oladele Aderibibge |
| author_sort | Aya-Ebi Okubo Eneni |
| collection | DOAJ |
| description | Schizophrenia is a major neuropsychiatric disorder associated with neurochemical perturbations characterized by behavioral abnormalities, for which effective treatment remains elusive. The current study investigated the neurotransmitter modulatory effect of diosmin in preventing and reversing ketamine-induced neurochemical and oxidative perturbations in mice. In the preventive study, mice were first treated with diosmin (50 mg/kg, i.p.) or risperidone (0.5 mg/kg) for 14-days before ketamine (20 mg/kg, i.p.) administration from the 8th-14th day. However, in the reversal approach, mice were injected with ketamine (20 mg/kg, i.p.) for 14 days before treatment with diosmin (50 mg/kg, i.p.) or risperidone from days 8–14. Behavioral consequences were measured using open-field, Y-maze, forced-swim, and social interaction tests. Neurochemical and oxidative changes critical to the disease were characterized in the striatum, prefrontal cortex and hippocampus. Diosmin improved the behavioral abnormalities and improved memory in ketamine-treated mice. Also, diosmin prevented and reversed ketamine-induced oxidative stress, evidenced by increased glutathione and superoxide-dismutase with a profound decrease in malondialdehyde levels in the striatum, prefrontal-cortex and hippocampus. Additionally, diosmin reduced nitrite levels in the striatum in the preventive approach, but with a significant decrease in the striatum and prefrontal-cortex compared to ketamine groups. Ketamine-induced increased acetylcholinesterase activity in the hippocampus and prefrontal-cortex were both prevented and reversed significantly. Lastly, ketamine-induced dopamine, serotonin and glutamate dysregulations in the striatum, prefrontal-cortex and hippocampus were prevented and reversed by diosmin compared to ketamine controls. Conclusively, diosmin improved ketamine-induced neurobehavioral deficits by augmenting antioxidant systems and modulating neurotransmitters in mice brains. |
| format | Article |
| id | doaj-art-a0b23ef06f7e4d10aae36066876ae051 |
| institution | OA Journals |
| issn | 2666-4593 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Disorders |
| spelling | doaj-art-a0b23ef06f7e4d10aae36066876ae0512025-08-20T02:03:14ZengElsevierBrain Disorders2666-45932025-06-011810021010.1016/j.dscb.2025.100210Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychoticAya-Ebi Okubo Eneni0Benneth Ben-Azu1Abayomi Mayowa Ajayi2Adegbuyi Oladele Aderibibge3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta State University, Abraka, Delta State, Nigeria; Neuropharmacology Unit, department of Pharmacology and Therapeutics, Faculty of Basic Medica Science, College of Medicine, University of Ibadan, Oyo state, Nigeria; Corresponding author at: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta State University, Abraka, Nigeria.DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria; Neuropharmacology Unit, department of Pharmacology and Therapeutics, Faculty of Basic Medica Science, College of Medicine, University of Ibadan, Oyo state, Nigeria; Corresponding author at: DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.Neuropharmacology Unit, department of Pharmacology and Therapeutics, Faculty of Basic Medica Science, College of Medicine, University of Ibadan, Oyo state, NigeriaNeuropharmacology Unit, department of Pharmacology and Therapeutics, Faculty of Basic Medica Science, College of Medicine, University of Ibadan, Oyo state, NigeriaSchizophrenia is a major neuropsychiatric disorder associated with neurochemical perturbations characterized by behavioral abnormalities, for which effective treatment remains elusive. The current study investigated the neurotransmitter modulatory effect of diosmin in preventing and reversing ketamine-induced neurochemical and oxidative perturbations in mice. In the preventive study, mice were first treated with diosmin (50 mg/kg, i.p.) or risperidone (0.5 mg/kg) for 14-days before ketamine (20 mg/kg, i.p.) administration from the 8th-14th day. However, in the reversal approach, mice were injected with ketamine (20 mg/kg, i.p.) for 14 days before treatment with diosmin (50 mg/kg, i.p.) or risperidone from days 8–14. Behavioral consequences were measured using open-field, Y-maze, forced-swim, and social interaction tests. Neurochemical and oxidative changes critical to the disease were characterized in the striatum, prefrontal cortex and hippocampus. Diosmin improved the behavioral abnormalities and improved memory in ketamine-treated mice. Also, diosmin prevented and reversed ketamine-induced oxidative stress, evidenced by increased glutathione and superoxide-dismutase with a profound decrease in malondialdehyde levels in the striatum, prefrontal-cortex and hippocampus. Additionally, diosmin reduced nitrite levels in the striatum in the preventive approach, but with a significant decrease in the striatum and prefrontal-cortex compared to ketamine groups. Ketamine-induced increased acetylcholinesterase activity in the hippocampus and prefrontal-cortex were both prevented and reversed significantly. Lastly, ketamine-induced dopamine, serotonin and glutamate dysregulations in the striatum, prefrontal-cortex and hippocampus were prevented and reversed by diosmin compared to ketamine controls. Conclusively, diosmin improved ketamine-induced neurobehavioral deficits by augmenting antioxidant systems and modulating neurotransmitters in mice brains.http://www.sciencedirect.com/science/article/pii/S2666459325000307PsychosisAntipsychoticDopamineKetamineOxidative stressNegative symptoms |
| spellingShingle | Aya-Ebi Okubo Eneni Benneth Ben-Azu Abayomi Mayowa Ajayi Adegbuyi Oladele Aderibibge Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic Brain Disorders Psychosis Antipsychotic Dopamine Ketamine Oxidative stress Negative symptoms |
| title | Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic |
| title_full | Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic |
| title_fullStr | Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic |
| title_full_unstemmed | Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic |
| title_short | Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic |
| title_sort | ketamine induced behavioral perturbations redox imbalances and neurotransmitter deficits in mice the preventive and reversal neuromodulatory potential of diosmin as an antipsychotic |
| topic | Psychosis Antipsychotic Dopamine Ketamine Oxidative stress Negative symptoms |
| url | http://www.sciencedirect.com/science/article/pii/S2666459325000307 |
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