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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2025-07-01
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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. |
| format | Article |
| id | doaj-art-0853466216064dddbe1d784a695eb35e |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Biomedicines |
| 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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