Effect of NR2B antagonist on behavior and related signal proteins in a rat model of levodopa-induced motor complications
10.3760/cma.j.issn.1674-6554.2011.11.003
- VernacularTitle:N-甲基-D-天冬氨酸受体2B亚基拮抗剂对帕金森病运动并发症大鼠行为及相关信号蛋白的影响
- Author:
Maowen BA
;
Min KONG
;
Xuwen SUN
;
Xiaotong WANG
- Publication Type:Journal Article
- Keywords:
Parkinson' disease;
Motor complication;
N-methyl-D-aspartate acid receptor subunit 2B
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2011;20(11):967-969
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the role of N-methyl-D-aspartate receptor subunit 2B (NR2B) antagonist CP-101.606 in behaviour and expression of related signal proteins in a rat model of levodopa-induced motor complications.MethodsThe hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle.Then,rats were intraperitoneally treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg,twice daily) for 22 days.On 23th day,rats received CP-101.606 before levodopa administration.Rotational duration was estimated.After sacrificed,phosphorylated NR2B and Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and glutamate receptor 1 ( GluR1S831 ) were observed by western blot.ResultsThe results showed that NR2B antagonist CP-101.606 reversed the levodopa-induced shortened rotational duration.Chronic levodopa treatment increased abundance of the phosphorylated NR2B and downstream related signal proteins CaMKⅡ and GluR1S831 to (145.3±6.5)％ and (132.5±5.7)％ and (105.6±6.3)％,respectively.Moreover,CP-101.606 could reduce hyperphosphorylation of NR2B and CaMKⅡ and GluR1 S831 to (102 ± 4.9 )％,(98.4±3.9)％ and (49.5 ± 4.2 )％,respectively.ConclusionsThese results indicate that the enhancement of N-methyl-D-aspartate (NMDA) receptor function mediated by NR2B phosphorylation contribute to development of motor complications,through a mechanism that involved the downstream signal mediators of NMDA receptor overactivation.Pharmaceuticals which act to inhibit NR2B may be useful in the treatment of the motor complications in parkinsonian patients.
