Abstract
In the recent years, the serotonin system has emerged as a key player in the induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson’s disease. In fact, serotonin neurons possess the enzymatic machinery able to convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and release. However, serotonin neurons lack a feedback control mechanism able to regulate synaptic DA levels. While in a situation of partial DA depletion spared DA terminals can buffer DA released from serotonin neurons, the progression of DA neuron degeneration impairs this protective mechanism, causing swings in synaptic DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID in animal models of Parkinson’s disease. In this article, we will revise the experimental evidence pointing to the important role of serotonin neurons in dyskinesia, and we will discuss the clinical implications.
Highlights
In the recent years, the serotonin system has emerged as a key player in the induction of L-DOPA-induced dyskinesia (LID) in animal models of Parkinson’s disease
It has been shown that delaying the initiation of the l-DOPA administration, while postpones the onset of dyskinesia compared to lDOPA monotherapy, does not reduce the severity of dyskinesia once l-DOPA is introduced [4]
In a positron emission tomography (PET) study, it has been demonstrated that dyskinetic patients present higher synaptic DA levels 1 h after administration of l-DOPA compared to stable responders [5]
Summary
The serotonin system has emerged as a key player in the induction of L-DOPA-induced dyskinesia (LID) in animal models of Parkinson’s disease. THE SEROTONERGIC SYSTEM IN LID: PRE-CLINICAL EVIDENCE the efficacy of the treatment is partly compromised in advanced stage of disease, as it is in animal models of complete DA denervation, l-DOPA still produces clear motor effects, of which dyskinesias represent an abnormal manifestation; this suggests that other cellular compartments can substitute the lost DA neurons in mediating l-DOPA conversion to DA, and neurotransmitter release.
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