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Signaling Mechanisms in l-DOPA-Induced Dyskinesia

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The Basal Ganglia

Part of the book series: Innovations in Cognitive Neuroscience ((Innovations Cogn.Neuroscience))

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Abstract

l-DOPA-induced dyskinesia is a major complication of dopamine replacement therapy in Parkinson’s disease. Clinical and experimental studies indicate that this complication develops because of a substantial loss of dopaminergic afferents to the motor part of the striatum, causing both pre- and postsynaptic changes in the nigrostriatal system. Moreover, a number of non-dopaminergic neurotransmitters modulate both the risk and the severity of this motor complication of treatment. This chapter reviews molecular changes occurring in the dopamine-denervated striatum in animal models of l-DOPA-induced dyskinesia, which have been partly verified by human studies. We will review a wide scope of alterations ranging from the phenomenon of dopamine D1 receptor supersensitivity (which is key to abnormal signaling responses in striatal neurons) to the role played by glutamate receptors and the altered regulation of gene and protein expression. We will finally review the evidence for a gliovascular contribution to the pathogenesis of l-DOPA-induced dyskinesia. It is our hope that the pathophysiological insights derived from animal models of l-DOPA-induced dyskinesia will soon lead to new therapeutics for the suppression or prevention of this debilitating condition.

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  1. Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Sciences, Lund University, BMC F11, Lund, 221 84, Sweden

    Cristina Alcacer Ph.D., Veronica Francardo M.D. & M. Angela Cenci M.D., Ph.D.

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  1. Cristina Alcacer Ph.D.
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  2. Veronica Francardo M.D.
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  3. M. Angela Cenci M.D., Ph.D.
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    Jean-Jacques Soghomonian

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Alcacer, C., Francardo, V., Cenci, M.A. (2016). Signaling Mechanisms in l-DOPA-Induced Dyskinesia. In: Soghomonian, JJ. (eds) The Basal Ganglia. Innovations in Cognitive Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-42743-0_8

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