Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue

<b>Background</b>: Tramadol binds to opioid receptors and inhibits norepinephrine and serotonin reuptake, causing serotonin syndrome. Tianeptine stimulates serotonin reuptake and reduces serotonin levels. The aim of this study was to investigate whether tianeptine is effective against se...

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Main Authors: Irem Ates, Bahar Isik, Fusun Gozen, Gulce Naz Yazici, Mine Gulaboglu, Renad Mammadov, Gulbeniz Huseynova, Durdu Altuner, Halis Suleyman
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/7/1690
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author Irem Ates
Bahar Isik
Fusun Gozen
Gulce Naz Yazici
Mine Gulaboglu
Renad Mammadov
Gulbeniz Huseynova
Durdu Altuner
Halis Suleyman
author_facet Irem Ates
Bahar Isik
Fusun Gozen
Gulce Naz Yazici
Mine Gulaboglu
Renad Mammadov
Gulbeniz Huseynova
Durdu Altuner
Halis Suleyman
author_sort Irem Ates
collection DOAJ
description <b>Background</b>: Tramadol binds to opioid receptors and inhibits norepinephrine and serotonin reuptake, causing serotonin syndrome. Tianeptine stimulates serotonin reuptake and reduces serotonin levels. The aim of this study was to investigate whether tianeptine is effective against serotonin syndrome that may occur with serotoninergic drugs such as tramadol and citalopram. <b>Methods</b>: Rats were divided into eight groups (n = 6) that received tramadol (50 mg/kg), citalopram (10 mg/kg), or tianeptine (5 mg/kg) alone or a combination of tramadol + citalopram, tramadol + tianeptine, citalopram + tianeptine or tramadol + citalopram + tianeptine at the same doses administered to the stomach by oral gavage for 3 weeks. The healthy control group was given saline. Malondialdehyde, total glutathione, superoxide dismutase, and catalase levels were measured in removed brain tissues. The tissues were also examined histopathologically. <b>Results</b>: In the tramadol, tramadol + citalopram, and tramadol + citalopram + tianeptine groups, malondialdehyde levels were found to be higher compared to the control group, while glutathione, superoxide dismutase, and catalase levels were found to be lower. In other groups, values close to the control group were measured. Morphological degeneration was observed in neurons in the tramadol + citalopram group. The swelling of astrocytes and pericellular edema in oligodendrocytes were also observed. A significant population increase was noted in microglial cells. Blood vessels belonging to the tissue were observed to be severely dilated and congested. Histopathological damage was partially resolved in the group given tramadol + citalopram + tianeptine. <b>Conclusions</b>: The tramadol + citalopram combination caused severe oxidative stress in brain tissue. Tramadol alone caused mild damage in brain tissue, whereas tianeptine prevented the brain damage caused by tramadol.
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spelling doaj-art-0853466216064dddbe1d784a695eb35e2025-08-20T04:00:54ZengMDPI AGBiomedicines2227-90592025-07-01137169010.3390/biomedicines13071690Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain TissueIrem Ates0Bahar Isik1Fusun Gozen2Gulce Naz Yazici3Mine Gulaboglu4Renad Mammadov5Gulbeniz Huseynova6Durdu Altuner7Halis Suleyman8Department of Anesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum 25240, TurkeyDepartment of Emergency Medicine, Faculty of Medicine, Ataturk University, Erzurum 25240, TurkeyDepartment of Anesthesiology and Reanimation, Bursa High Specialization Training and Research Hospital, University of Health Sciences, Bursa 16310, TurkeyDepartment of Histology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, TurkeyDepartment of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum 25240, TurkeyDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, TurkeyDepartment of Pharmacology, Azerbaijan Medical University, Baku AZ1022, AzerbaijanDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, TurkeyDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Turkey<b>Background</b>: Tramadol binds to opioid receptors and inhibits norepinephrine and serotonin reuptake, causing serotonin syndrome. Tianeptine stimulates serotonin reuptake and reduces serotonin levels. The aim of this study was to investigate whether tianeptine is effective against serotonin syndrome that may occur with serotoninergic drugs such as tramadol and citalopram. <b>Methods</b>: Rats were divided into eight groups (n = 6) that received tramadol (50 mg/kg), citalopram (10 mg/kg), or tianeptine (5 mg/kg) alone or a combination of tramadol + citalopram, tramadol + tianeptine, citalopram + tianeptine or tramadol + citalopram + tianeptine at the same doses administered to the stomach by oral gavage for 3 weeks. The healthy control group was given saline. Malondialdehyde, total glutathione, superoxide dismutase, and catalase levels were measured in removed brain tissues. The tissues were also examined histopathologically. <b>Results</b>: In the tramadol, tramadol + citalopram, and tramadol + citalopram + tianeptine groups, malondialdehyde levels were found to be higher compared to the control group, while glutathione, superoxide dismutase, and catalase levels were found to be lower. In other groups, values close to the control group were measured. Morphological degeneration was observed in neurons in the tramadol + citalopram group. The swelling of astrocytes and pericellular edema in oligodendrocytes were also observed. A significant population increase was noted in microglial cells. Blood vessels belonging to the tissue were observed to be severely dilated and congested. Histopathological damage was partially resolved in the group given tramadol + citalopram + tianeptine. <b>Conclusions</b>: The tramadol + citalopram combination caused severe oxidative stress in brain tissue. Tramadol alone caused mild damage in brain tissue, whereas tianeptine prevented the brain damage caused by tramadol.https://www.mdpi.com/2227-9059/13/7/1690tramadolcitalopramtianeptineratbrain
spellingShingle Irem Ates
Bahar Isik
Fusun Gozen
Gulce Naz Yazici
Mine Gulaboglu
Renad Mammadov
Gulbeniz Huseynova
Durdu Altuner
Halis Suleyman
Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
Biomedicines
tramadol
citalopram
tianeptine
rat
brain
title Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
title_full Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
title_fullStr Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
title_full_unstemmed Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
title_short Investigation into the Effects of Tramadol, Citalopram, Tianeptine, and Their Combinations on Rat Brain Tissue
title_sort investigation into the effects of tramadol citalopram tianeptine and their combinations on rat brain tissue
topic tramadol
citalopram
tianeptine
rat
brain
url https://www.mdpi.com/2227-9059/13/7/1690
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