β-arrestin1 mediates the effect of MK-801 on levodopa-induced dyskinesia in Parkinson ', s disease / 中华神经科杂志

ABSTRACT

ObjectiveTo investigate the effect of MK-801 on levodopa-induced dyskinesia (LID)in Parkinson' s disease (PD). MethodsRat models ( n = 25) of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia (LID) group (n = 10), MK801 treatment group (n = 10) and PD group (n =5). Another 5 rats were served as control group. The behaviors of LID rats treated with MK-801 were observed. Immunohistochemistry and Western blot analysis were used to determine the expression of β-arrestin1 in the striate of rats.Results After MK-801 treatment, abnormalinvoluntarymovementscores and peakturning weredecreasedin LIDrats.Immunohistochemistry showed that β-arrestin1-positive cells of the lesioned side ((2. 95 ± 0. 44) × 104) in LID rats were decreased compared to the contralateral side ( ( 3.78 ± 0. 37 ) × 104, t = 5. 415, P ＜ 0. 05 ).Western blot showed that the levels of β-arrestinl in PD group ( presented as lesioned side/contralateral side) were ( 81.02％ ± 2. 23％ ). The levels of β-arrestin1 (64. 88％ ± 3. 10％ ) were deceased in LID rats compared to PD rats ( t = 9.47, P ＜ 0. 01 ). However, the levels of β-arrestin1 ( 89. 26％ ± 1.90％ )were increased in MK-801-treated rats (t = 14. 82, P ＜0. 01). ConclusionsMK-801 reduces LID in PD rats. The beneficial effect of MK-801 may be mediated through the increased expression of β-arrestinl which in turninhibits the overactivation of glutamate receptors.