Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors
<b>Background/Objectives:</b> In post-traumatic stress disorder (PTSD), anxiety-like symptoms are often associated with elevated noradrenaline levels and decreased serotonin. Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat anxiety, but elevated serotonin has...
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2024-10-01
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| author | Vadim E. Tseilikman Olga B. Tseilikman Marina N. Karpenko Dmitrii S. Traktirov Daria A. Obukhova Vladislav A. Shatilov Maxim S. Zhukov Gennady V. Manuilov Oleg N. Yegorov Maxim R. Aristov Ilya A. Lipatov Irina A. Buksha Alexandr E. Epitashvili Anton A. Pashkov Jurica Novak |
| author_facet | Vadim E. Tseilikman Olga B. Tseilikman Marina N. Karpenko Dmitrii S. Traktirov Daria A. Obukhova Vladislav A. Shatilov Maxim S. Zhukov Gennady V. Manuilov Oleg N. Yegorov Maxim R. Aristov Ilya A. Lipatov Irina A. Buksha Alexandr E. Epitashvili Anton A. Pashkov Jurica Novak |
| author_sort | Vadim E. Tseilikman |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> In post-traumatic stress disorder (PTSD), anxiety-like symptoms are often associated with elevated noradrenaline levels and decreased serotonin. Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat anxiety, but elevated serotonin has been observed in some anxiety disorders. This study investigates stress-induced anxiety as an immediate effect of chronic stress exposure using the predator stress paradigm. <b>Methods:</b> We examined serotonin levels, serotonin transporter (SERT), and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mn>3</mn><mi>A</mi></mrow></msub></semantics></math></inline-formula> receptor gene expression in response to stress. The effects of SSRIs (paroxetine, sertraline) and resveratrol on these parameters were also analyzed, alongside co-treatment with resveratrol and sertraline. <b>Results:</b> Chronic stress exposure led to a significant increase in serotonin levels and upregulation of SERT and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>3</mn><mi>A</mi></mrow></semantics></math></inline-formula> receptor expression. SSRIs failed to prevent anxiety or reduce serotonin levels, partly due to suppressed SERT expression. Resveratrol downregulated SERT and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>3</mn><mi>A</mi></mrow></semantics></math></inline-formula> expression less than SSRIs but effectively reduced anxiety and restored serotonin, likely by upregulating MAO-A expression. Co-treatment with resveratrol and sertraline produced the strongest anxiolytic effect. <b>Conclusions:</b> Elevated serotonin and increased expression of SERT and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mn>3</mn><mi>A</mi></mrow></msub></semantics></math></inline-formula> receptor genes are key factors in stress-related anxiety. Resveratrol and SSRIs target these mechanisms, suggesting potential therapeutic strategies for anxiety disorders. Future research will focus on further elucidating the serotonergic mechanisms involved and identifying new anxiolytic drug targets. |
| format | Article |
| id | doaj-art-68deddff70164d609d86141359f06efc |
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| issn | 2227-9059 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-68deddff70164d609d86141359f06efc2025-08-20T02:08:12ZengMDPI AGBiomedicines2227-90592024-10-011211245510.3390/biomedicines12112455Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake InhibitorsVadim E. Tseilikman0Olga B. Tseilikman1Marina N. Karpenko2Dmitrii S. Traktirov3Daria A. Obukhova4Vladislav A. Shatilov5Maxim S. Zhukov6Gennady V. Manuilov7Oleg N. Yegorov8Maxim R. Aristov9Ilya A. Lipatov10Irina A. Buksha11Alexandr E. Epitashvili12Anton A. Pashkov13Jurica Novak14Higher Medical and Biological School, South Ural State University, 454080 Chelyabinsk, RussiaHigher Medical and Biological School, South Ural State University, 454080 Chelyabinsk, RussiaPavlov Department of Physiology, Institute of Experimental Medicine, 197376 Saint Petersburg, RussiaPavlov Department of Physiology, Institute of Experimental Medicine, 197376 Saint Petersburg, RussiaPavlov Department of Physiology, Institute of Experimental Medicine, 197376 Saint Petersburg, RussiaHigher Medical and Biological School, South Ural State University, 454080 Chelyabinsk, RussiaFaculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, RussiaHigher Medical and Biological School, South Ural State University, 454080 Chelyabinsk, RussiaFaculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, RussiaFaculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, RussiaFaculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, RussiaFaculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, RussiaFaculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, RussiaFederal Neurosurgical Center, 630048 Novosibirsk, RussiaCentre for Informatics and Computing, Ruđer Bošković Institute, 10000 Zagreb, Croatia<b>Background/Objectives:</b> In post-traumatic stress disorder (PTSD), anxiety-like symptoms are often associated with elevated noradrenaline levels and decreased serotonin. Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat anxiety, but elevated serotonin has been observed in some anxiety disorders. This study investigates stress-induced anxiety as an immediate effect of chronic stress exposure using the predator stress paradigm. <b>Methods:</b> We examined serotonin levels, serotonin transporter (SERT), and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mn>3</mn><mi>A</mi></mrow></msub></semantics></math></inline-formula> receptor gene expression in response to stress. The effects of SSRIs (paroxetine, sertraline) and resveratrol on these parameters were also analyzed, alongside co-treatment with resveratrol and sertraline. <b>Results:</b> Chronic stress exposure led to a significant increase in serotonin levels and upregulation of SERT and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>3</mn><mi>A</mi></mrow></semantics></math></inline-formula> receptor expression. SSRIs failed to prevent anxiety or reduce serotonin levels, partly due to suppressed SERT expression. Resveratrol downregulated SERT and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>3</mn><mi>A</mi></mrow></semantics></math></inline-formula> expression less than SSRIs but effectively reduced anxiety and restored serotonin, likely by upregulating MAO-A expression. Co-treatment with resveratrol and sertraline produced the strongest anxiolytic effect. <b>Conclusions:</b> Elevated serotonin and increased expression of SERT and 5-HT<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msub><mrow></mrow><mrow><mn>3</mn><mi>A</mi></mrow></msub></semantics></math></inline-formula> receptor genes are key factors in stress-related anxiety. Resveratrol and SSRIs target these mechanisms, suggesting potential therapeutic strategies for anxiety disorders. Future research will focus on further elucidating the serotonergic mechanisms involved and identifying new anxiolytic drug targets.https://www.mdpi.com/2227-9059/12/11/2455chronic stressresveratrolnoradrenalineserotonindopaminehippocampus |
| spellingShingle | Vadim E. Tseilikman Olga B. Tseilikman Marina N. Karpenko Dmitrii S. Traktirov Daria A. Obukhova Vladislav A. Shatilov Maxim S. Zhukov Gennady V. Manuilov Oleg N. Yegorov Maxim R. Aristov Ilya A. Lipatov Irina A. Buksha Alexandr E. Epitashvili Anton A. Pashkov Jurica Novak Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors Biomedicines chronic stress resveratrol noradrenaline serotonin dopamine hippocampus |
| title | Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors |
| title_full | Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors |
| title_fullStr | Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors |
| title_full_unstemmed | Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors |
| title_short | Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors |
| title_sort | unraveling the serotonergic mechanism of stress related anxiety focus on co treatment with resveratrol and selective serotonin reuptake inhibitors |
| topic | chronic stress resveratrol noradrenaline serotonin dopamine hippocampus |
| url | https://www.mdpi.com/2227-9059/12/11/2455 |
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