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 the activity of striatal protein kinase A (PKA) and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). In this study, we showed that systemic administration of the cannabinoid agonist WIN55212-2 ameliorated L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-OHDA rat model of PD and reversed L-DOPA-induced PKA hyperactivity via a CB(1)-mediated mechanism. This effect was accompanied by increased phosphorylation of DARPP-32 at threonine 34, which was partially blocked by CB(1) antagonism. Striatal PKA activity was positively correlated with the severity of L-DOPA-induced axial and limb dyskinesias, suggesting a role for the cAMP/PKA signaling pathway in the expression of these motor disturbances. Our results indicate that activation of CB(1) receptors, as well as reduction of striatal PKA hyperactivity, might be an effective strategy for the treatment of L-DOPA-induced dyskinesias.

Autore Pugliese

• Trabace Luigia

Tutti gli autori

• A. Martinez , T. Macheda , MG. Morgese , L. Trabace , A. Giuffrida

Titolo volume/Rivista

NEUROSCIENCE RESEARCH

Anno di pubblicazione

2012

ISSN

0168-0102

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

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Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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