Additionally, a review [8] shows that highly soluble l-DOPA prodrugs may be effective in avoiding the in vivo blood concentration swings that potentially lead to motor fluctuations and dyskinesia.
Levodopa-induced dyskinesia has long been thought to arise through pathological alterations in pre-synaptic and post-synaptic signal transduction in the nigrostriatal pathway (dorsal striatum).
[4] In experiments employing real-time electrophysiological recordings in awake and active animals, LIDs have been shown to be strongly associated with cortical gamma-oscillations with accompanying Δc-fos overexpression, proposedly due to a dysregulation of dopamine signaling in the cortico-basal ganglia circuitry.
[10] ΔFosB overexpression in the dorsal striatum (nigrostriatal dopamine pathway) via viral vectors generates levodopa-induced dyskinesia in animal models of Parkinson's disease.
[12] Levetiracetam, an antiepileptic drug which has been demonstrated to reduce the severity of levodopa-induced dyskinesias, has been shown to dose-dependently decrease the induction of dorsal striatal ΔFosB expression in rats when co-administered with levodopa.