The cannabinoid agonist WIN55212-2 decreases l-DOPA-induced PKA activation and dyskinetic behavior in 6-OHDA-treated rats
作者： Alex Martinez , Teresa Macheda , Maria Grazia Morgese , Luigia Trabace , Andrea Giuffrida
DOI: 10.1016/J.NEURES.2011.12.006
关键词:
摘要: Abstract Chronic Levodopa ( l -DOPA), the gold standard therapy for Parkinson's disease (PD), causes disabling motor complications (dyskinesias) that are associated with changes in activity of striatal protein kinase A (PKA) and cAMP-regulated phosphoprotein 32 kDa (DARPP-32). In this study, we showed systemic administration cannabinoid agonist WIN55212-2 ameliorated -DOPA-induced abnormal involuntary movements (AIMs) 6-OHDA rat model PD reversed PKA hyperactivity via a CB1-mediated mechanism. This effect was accompanied by increased phosphorylation DARPP-32 at threonine 34, which partially blocked CB1 antagonism. Striatal positively correlated severity axial limb dyskinesias, suggesting role cAMP/PKA signaling pathway expression these disturbances. Our results indicate activation receptors, as well reduction hyperactivity, might be an effective strategy treatment dyskinesias.
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