Serotonergic involvement in levodopa-induced dyskinesias in Parkinson’s disease

Levodopa-induced dyskinesias (LID) represent a substantial barrier to effective symptomatic management of Parkinson’s disease, but current treatment options for this debilitating side effect are limited, despite an increasing understanding of their pathophysiology from animal models. Increasing evidence suggests that serotonin neurons have a pivotal role in the induction and maintenance of dyskinesias, and provide a promising target for anti-dyskinetic therapies. Here, we review the evidence for serotonergic involvement in dyskinesias from animal and human data, and highlight some of the translational gaps which may explain why the success of serotonin autoreceptor agonists as anti-dyskinetic agents in experimental models has failed to be replicated in clinical trials.