Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia
Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor symptoms that result from loss of nigrostriatal dopamine (DA) cells. While L-DOPA provides symptom alleviation, its chronic use often results in the development of L-DOPA-induced dyskinesia (LID). Evidence suggests that...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/6/837 |
| _version_ | 1797612846300790784 |
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| author | Carla Budrow Kayla Elder Michael Coyle Ashley Centner Natalie Lipari Sophie Cohen John Glinski N’Senga Kinzonzi Emily Wheelis Grace McManus Fredric Manfredsson Christopher Bishop |
| author_facet | Carla Budrow Kayla Elder Michael Coyle Ashley Centner Natalie Lipari Sophie Cohen John Glinski N’Senga Kinzonzi Emily Wheelis Grace McManus Fredric Manfredsson Christopher Bishop |
| author_sort | Carla Budrow |
| collection | DOAJ |
| description | Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor symptoms that result from loss of nigrostriatal dopamine (DA) cells. While L-DOPA provides symptom alleviation, its chronic use often results in the development of L-DOPA-induced dyskinesia (LID). Evidence suggests that neuroplasticity within the serotonin (5-HT) system contributes to LID onset, persistence, and severity. This has been supported by research showing 5-HT compounds targeting 5-HT<sub>1A/1B</sub> receptors and/or the 5-HT transporter (SERT) can reduce LID. Recently, vortioxetine, a multimodal 5-HT compound developed for depression, demonstrated acute anti-dyskinetic effects. However, the durability and underlying pharmacology of vortioxetine’s anti-dyskinetic actions have yet to be delineated. To address these gaps, we used hemiparkinsonian rats in Experiment 1, examining the effects of sub-chronic vortioxetine on established LID and motor performance. In Experiment 2, we applied the 5-HT<sub>1A</sub> antagonist WAY-100635 or 5-HT<sub>1B</sub> antagonist SB-224289 in conjunction with L-DOPA and vortioxetine to determine the contributions of each receptor to vortioxetine’s effects. The results revealed that vortioxetine consistently and dose-dependently attenuated LID while independently, 5-HT<sub>1A</sub> and 5-HT<sub>1B</sub> receptors each partially reversed vortioxetine’s effects. Such findings further support the promise of pharmacological strategies, such as vortioxetine, and indicate that broad 5-HT actions may provide durable responses without significant side effects. |
| first_indexed | 2024-03-11T06:47:45Z |
| format | Article |
| id | doaj.art-874e04ed7cf0486c9e0cdb0bba160b35 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T06:47:45Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-874e04ed7cf0486c9e0cdb0bba160b352023-11-17T10:12:33ZengMDPI AGCells2073-44092023-03-0112683710.3390/cells12060837Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced DyskinesiaCarla Budrow0Kayla Elder1Michael Coyle2Ashley Centner3Natalie Lipari4Sophie Cohen5John Glinski6N’Senga Kinzonzi7Emily Wheelis8Grace McManus9Fredric Manfredsson10Christopher Bishop11Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USADepartment of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USABehavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USAParkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor symptoms that result from loss of nigrostriatal dopamine (DA) cells. While L-DOPA provides symptom alleviation, its chronic use often results in the development of L-DOPA-induced dyskinesia (LID). Evidence suggests that neuroplasticity within the serotonin (5-HT) system contributes to LID onset, persistence, and severity. This has been supported by research showing 5-HT compounds targeting 5-HT<sub>1A/1B</sub> receptors and/or the 5-HT transporter (SERT) can reduce LID. Recently, vortioxetine, a multimodal 5-HT compound developed for depression, demonstrated acute anti-dyskinetic effects. However, the durability and underlying pharmacology of vortioxetine’s anti-dyskinetic actions have yet to be delineated. To address these gaps, we used hemiparkinsonian rats in Experiment 1, examining the effects of sub-chronic vortioxetine on established LID and motor performance. In Experiment 2, we applied the 5-HT<sub>1A</sub> antagonist WAY-100635 or 5-HT<sub>1B</sub> antagonist SB-224289 in conjunction with L-DOPA and vortioxetine to determine the contributions of each receptor to vortioxetine’s effects. The results revealed that vortioxetine consistently and dose-dependently attenuated LID while independently, 5-HT<sub>1A</sub> and 5-HT<sub>1B</sub> receptors each partially reversed vortioxetine’s effects. Such findings further support the promise of pharmacological strategies, such as vortioxetine, and indicate that broad 5-HT actions may provide durable responses without significant side effects.https://www.mdpi.com/2073-4409/12/6/837levodopa-induced dyskinesiaParkinson’s diseaseserotonindopamineserotonin transporter5-HT<sub>1A</sub> receptor |
| spellingShingle | Carla Budrow Kayla Elder Michael Coyle Ashley Centner Natalie Lipari Sophie Cohen John Glinski N’Senga Kinzonzi Emily Wheelis Grace McManus Fredric Manfredsson Christopher Bishop Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia Cells levodopa-induced dyskinesia Parkinson’s disease serotonin dopamine serotonin transporter 5-HT<sub>1A</sub> receptor |
| title | Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia |
| title_full | Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia |
| title_fullStr | Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia |
| title_full_unstemmed | Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia |
| title_short | Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia |
| title_sort | broad serotonergic actions of vortioxetine as a promising avenue for the treatment of l dopa induced dyskinesia |
| topic | levodopa-induced dyskinesia Parkinson’s disease serotonin dopamine serotonin transporter 5-HT<sub>1A</sub> receptor |
| url | https://www.mdpi.com/2073-4409/12/6/837 |
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