Nitric oxide, a new player in L-DOPA-induced dyskinesia?

L-3,4-Dihydroxyphenylalanine (L-DOPA) remains the most effective symptomatic treatment of Parkinson's disease (PD). However, the long-term use of L-DOPA causes, in combination with disease progression, the development of motor complications termed L-DOPA-induced dyskinesia (LID). LID is the result of profound modifications in the functional organization of the basal ganglia circuitry. There is increasing evidence of the involvement of non-dopaminergic systems on the pathophysiology of LID. This raises the possibility of novel promising therapeutic approaches in the future, including agents that interfere with glutamatergic, serotonergic, adenosine, adrenergic, and cholinergic neurotransmission that are currently in preclinical testing or clinical development. Herein, we summarize the current knowledge of the pharmacology of LID in PD. More importantly, this review attempts to highlight the role of nitric oxide (NO) in PD and provide a comprehensive picture of recent preclinical findings from our group and others showing its potential involvement in dyskinesia.