mu- and delta-opioid receptor antagonists reduce levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease

Long-term treatment of Parkinson's disease with levodopa is complicated by the emergence of involuntary movements, known as levodopa-induced dyskinesi a. It has been hypothesized that increased opioid transmission in striatal output pathways may be responsible for the generation of dyskinesia. In thi s study, we have investigated the effect of blockade of opioid peptide tran smission on levodopa-induced dyskinesia in a primate model of Parkinson's d isease-the MPTP-lesioned marmoset. Coadministration of nonselective and mu- or delta -subtype-selective opioid receptor antagonists with levodopa resu lted in a significant decrease in dyskinesia. There was no attenuation of t he anti-parkinsonian actions of levodopa. These data suggest that specific mu- or delta -opioid receptor antagonists might be applicable clinically in the treatment of levodopa-induced dyskinesia in Parkinson's disease. (C) 2 001 Academic Press.