Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson's disease. Mov Disord 2010;25 Suppl

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 dyski-netic movements induced by repetitive, low doses of levo-dopa. Serotonin neurons have the capacity to store and release dopamine synthesized from systemically administered levodopa. However, because of the lack of any autoregula-tory feedback control, dopamine released from serotonin ter-minals results in excessive swings in extracellular dopamine levels after peripheral administration of levodopa. Such ‘‘dys-regulated’ ’ release of levodopa-derived dopamine is likely to be responsible for the appearance of the abnormal move-ments 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 Key words: dyskinesia; L-dopa; serotonin; 5-HT1A receptor agonist; 5-HT1B receptor agonist; graft-induced dyskinesi