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Serotonergic targets for the treatment of l-DOPA-induced dyskinesia

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

Dopamine (DA) replacement therapy with l-3,4-dihydroxyphenylalanine (l-DOPA) continues to be the gold-standard treatment for Parkinson’s disease (PD). Despite clear symptomatic benefit, long-term l-DOPA use often results in the development of l-DOPA-induced dyskinesia (LID), significantly reducing quality of life and increasing costs for PD patients and their caregivers. Accumulated research has demonstrated that several pre- and post-synaptic mechanisms contribute to LID development and expression. In particular, raphe-striatal hyperinnervation and unregulated DA release from 5-HT terminals is postulated to play a central role in LID manifestation. As such, manipulation of the 5-HT system has garnered considerable attention. Both pre-clinical and clinical research has supported the potential of modulating the 5-HT system for LID prevention and treatment. This review discusses the rationale for continued investigation of several potential anti-dyskinetic strategies including 5-HT stimulation of 5-HT1A and 5-HT1B receptors and blockade of 5-HT2A receptors and SERT. We present the latest findings from experimental and clinical investigations evaluating these 5-HT targets with the goal of identifying those with translational promise and the challenges associated with each.

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Thank you to Carolyn Saito for her constructive feedback on this manuscript.

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  1. Behavioral Neuroscience Program, Department of Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA

    Kathryn Lanza & Christopher Bishop

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Lanza, K., Bishop, C. Serotonergic targets for the treatment of l-DOPA-induced dyskinesia. J Neural Transm 125, 1203–1216 (2018). https://doi.org/10.1007/s00702-017-1837-1

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