Frontiers in Pharmacology (Jun 2019)
Levodopa/Benserazide PLGA Microsphere Prevents L-Dopa–Induced Dyskinesia via Lower β-Arrestin2 in 6-Hydroxydopamine Parkinson’s Rats
Abstract
Prolonged pulsatile administration of Levodopa (L-dopa) can generate L-dopa–induced dyskinesia (LID). Numerous research has reported that continuous dopamine delivery (CDD) was useful in reducing the severity of LID. 6-OHDA lesioned rats were divided into two groups to receive intermittent L-dopa stimulation (L-dopa/benserazide) or Levodopa/benserazide PLGA microsphere (LBPM) for 3 weeks. rAAV (recombinant adeno-associated virus) vector was used to overexpress and ablation of β-arrestin2. We found that LBPM developed less AIM severity compared with standard L-dopa administration, whereas selective deletion of β-arrestin2 in striatum neurons dramatically enhanced the severity of dyskinesia by LBPM. On the contrary, the effects of LBPM in terms of ALO AIM were further relieved by β-arrestin2 overexpression. Furthermore, no significant change in motor behavior was seen either in inhibition or overexpression of β-arrestin2. In short, our experiments provided evidence that LBPM’s prevention of LID behavior was likely due to β-arrestin2, suggesting that a therapy modulating β-arrestin2 may offer a more efficient anti-dyskinetic method with a low risk of untoward effects.
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