L-3, 4-dihydroxyphenylalanine (L-dopa) is the gold standard for symptomatic 
treatment of Parkinson's disease (PD), but long-term therapy is associated with 
the emergence of L-dopa-induced dyskinesia (LID). In the present study, L-dopa 
and benserazide were loaded by poly (lactic-co-glycolic acid) microspheres 
(LBM), which can release levodopa and benserazide in a sustained manner in order 
to continuous stimulate dopaminergic receptors. We investigated the role of 
striatal DR1/PKA/P-tau signal transduction in the molecular event underlying LID 
in the 6-OHDA-lesioned rat model of PD. We found that animals rendered 
dyskinetic by L-dopa treatment, administration of LBM prevented the severity of 
AIM score, as well as improvement in motor function. Moreover, we also showed 
L-dopa elicits profound alterations in the activity of three LID molecular 
markers, namely DR1/PKA/P-tau (ser396). These modifications are totally 
prevented by LBM treatment, a similar way to achieve continuous dopaminergic 
delivery (CDD). In conclusion, our experiments provided evidence that 
intermittent administration of L-dopa, but not continuous delivery, and 
DR1/PKA/p-tau (ser396) activation played a critical role in the molecular and 
behavioural induction of LID in 6-OHDA-lesioned rats. In addition, LBM treatment 
prevented the development of LID by inhibiting the expression of DR1/PKA/p-tau, 
as well as PPEB mRNA in dyskintic rats.