Exp Neurobiol 2016; 25(4): 174-184
Published online August 31, 2016
© The Korean Society for Brain and Neural Sciences
Hye-Yeon Park1,2, Young-Kyoung Ryu1, Jun Go1, Eunjung Son2, Kyoung-Shim Kim1,3*and Mee Ree Kim2*
1Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, 2Department of Food and Nutrition, Chung-Nam National University, Daejeon 34134, 3University of Science and Technology, Daejeon 34113, Korea
Correspondence to: *To whom correspondence should be addressed.
Mee Ree Kim, TEL: 82-42-821-6837, FAX: 82-42-821-8827
Kyoung-Shim Kim, TEL: 82-42-860-4634, FAX: 82-42-860-4609
L-3,4-dihydroxyphenylalanine (L-DOPA) is the most common treatment for patients with Parkinson's disease (PD). However, long term use of L-DOPA for PD therapy lead to abnormal involuntary movements (AIMs) known as dyskinesia. Fatty acid amide hydrolase (FAAH) is enriched protein in basal ganglia, and inhibition of the protein reduces dyskinetic behavior of mice. Palmitoyl serotonin (PA-5HT) is a hybrid molecule patterned after arachidonoyl serotonin, antagonist of FAAH. However, the effect of PA-5HT on L-DOPA-induced dyskinesia (LID) in PD have not yet been elucidated. To investigate whether PA-5HT relieve LID in PD and decrease hyperactivation of dopamine D1 receptors, we used the 6-hydroxydopomine (6-OHDA)-lesioned mouse model of PD and treated the L-DOPA (20 mg/kg) for 10 days with PA-5HT (0.3 mg/kg/day). The number of wall contacts with the forelimb in the cylinder test was significantly decreased by 6-OHDA lesion in mice and the pharmacotherapeutic effect of L-DOPA was also revealed in PA-5HT-treated mice. Moreover, in AIMs test, PA-5HT-treated mice showed significant reduction of locomotive, axial, limb, and orofacial AIMs score compared to the vehicle-treated mice. LID-induced hyper-phosphorylation of ERK1/2 and overexpression of FosB/ΔFosB was markedly decreased in 6-OHDA-lesioned striatum of PA-5HT-treated mice, indicating that PA-5HT decreased the dopamine D1 receptor-hyperactivation induced by chronic treatment of L-DOPA in dopamine-denervated striatum. These results suggest that PA-5HT effectively attenuates the development of LID and enhance of ERK1/2 phosphorylation and FosB/ΔFosB expression in the hemi-parkinsonian mouse model. PA-5HT may have beneficial effect on the LID in PD.
Keywords: palmitoyl serotonin, L-DOPA-induced dyskinesia, Parkinson’s disease, pERK1/2, FosB/ΔFosB