Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson's disease

Authors

  • Manolo Carta PhD,

    1. Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden
    2. Brain Repair and Imaging in Neural Systems Unit, Section for Neuroscience, Department of Experimental Medical Science, Lund University, Lund, Sweden
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  • Thomas Carlsson PhD,

    1. Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden
    2. Brain Repair and Imaging in Neural Systems Unit, Section for Neuroscience, Department of Experimental Medical Science, Lund University, Lund, Sweden
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  • Ana Muñoz PhD,

    1. Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden
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  • Deniz Kirik MD, PhD,

    1. Brain Repair and Imaging in Neural Systems Unit, Section for Neuroscience, Department of Experimental Medical Science, Lund University, Lund, Sweden
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  • Anders Björklund MD, PhD

    Corresponding author
    1. Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden
    • Lund University, Experimental Medical Science, Lund, Sweden
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  • Potential conflict of interest: Nothing to report.

Abstract

Recent studies in animal models of Parkinson's disease (PD) have provided evidence that dopamine released from spared serotonin afferents can act as a trigger of dyskinetic movements induced by repetitive, low doses of levodopa. Serotonin neurons have the capacity to store and release dopamine synthesized from systemically administered levodopa. However, because of the lack of any autoregulatory feedback control, dopamine released from serotonin terminals results in excessive swings in extracellular dopamine levels after peripheral administration of levodopa. Such “dysregulated” release of levodopa-derived dopamine is likely to be responsible for the appearance of the abnormal movements in levodopa-primed animals. This mechanism may also play a role in the development of graft-induced dyskinesias in patients that receive fetal neuron transplants, possibly due to the inclusion of serotonin neurons in the grafted ventral midbrain tissue, which contribute to maintain dopamine receptors of the denervated striatum in a supersensitive state. © 2010 Movement Disorder Society

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