Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia

Authors

Carla Budrow, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Kayla Elder, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Michael Coyle, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Ashley Centner, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Natalie Lipari, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Sophie Cohen, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
John Glinski, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
N'Senga Kinzonzi, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Emily Wheelis, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Grace McManus, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Fredric Manfredsson, Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USA.Follow
Christopher Bishop, Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.

Document Type

Article

Abstract

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 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 antagonist WAY-100635 or 5-HT 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 and 5-HT 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.

Keywords

5-HT1A receptor, 5-HT1B receptor, 6-hydroxydopamine, Parkinson’s disease, dopamine, levodopa-induced dyskinesia, serotonin, serotonin transporter, vortioxetine

Medical Subject Headings

Rats; Animals; Levodopa (adverse effects); Vortioxetine (pharmacology, therapeutic use); Serotonin; Rats, Sprague-Dawley; Dyskinesia, Drug-Induced (drug therapy)

Publication Date

3-8-2023

Publication Title

Cells

E-ISSN

2073-4409

Volume

12

Issue

6

PubMed ID

36980178

Digital Object Identifier (DOI)

10.3390/cells12060837

Recommended Citation

Budrow, Carla; Elder, Kayla; Coyle, Michael; Centner, Ashley; Lipari, Natalie; Cohen, Sophie; Glinski, John; Kinzonzi, N'Senga; Wheelis, Emily; McManus, Grace; Manfredsson, Fredric; and Bishop, Christopher, "Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia" (2023). Translational Neuroscience. 2243.
https://scholar.barrowneuro.org/neurobiology/2243