The serotonin system: a potential target for anti-dyskinetic treatments and biomarker discovery.

L-DOPA-induced dyskinesia is a major problem in the treatment of Parkinson's disease. Today there are few anti-dyskinetic treatments available for the patients, and all of them have major limitations. Recent findings have revealed an important role of the serotonin system in L-DOPA-induced dyskinesia. In the parkinsonian brain, serotonin axon terminals can compensate for the dopamine loss by converting L-DOPA into dopamine and releasing it as a false neurotransmitter. However, the terminals represent an aberrant source of dopamine release, increasing the risk for dyskinesia. In line with this, a relatively high density of serotonin axon fibres in striatum has been reported in dyskinetic animals and patients. Furthermore, serotonin can influence dyskinesia by modulating glutamate or GABA signalling in the basal ganglia via receptors located on non-serotonergic neurons. Through either mechanism, modulation of certain serotonin receptors has been shown to reduce the severity of dyskinetic movements. The serotonin system represents an interesting target for developing anti-dyskinetic treatments. Future therapies may take advantage of the synergistic effect produced by the modulation of different serotonin receptors or pursue a region-specific modulation of certain receptors. Moreover, morphological or biochemical features of the serotonin system could be used to develop biomarkers for patient stratification in clinical trials of anti-dyskinetic compounds.