The serotonergic system in levodopa-induced dyskinesia

An increasing body of experimental evidence suggests that serotonergic neurons play a major role in the production of levodopa-derived dopamine when dopaminergic neurons have degenerated, and that unregulated release of dopamine from serotonergic neurons is responsible for the appearance of levodopa-induced dyskinesia (LID) in animal models of Parkinson’s disease (PD). Promising preclinical findings show that the activation of 5-HT1 receptors, induced by the administration of 5-HT1A and/or 5-HT1B receptor agonists, suppressed LID in 6-OHDA-lesioned rat, as well as in MPTP-treated nonhuman primate models of PD, suggesting a possible clinical application. This chapter will provide an overview of these preclinical findings concerning the role of serotonergic neurons and serotonergic receptors in the appearance of LID, with a brief review of relevant clinical studies.