NR2B selective NMDA receptor antagonist CP-101,606 prevents levodopa-induced motor response alterations in hemi-parkinsonian rats.
NR2B selective NMDA receptor antagonist CP-101,606 prevents levodopa-induced motor response alterations in hemi-parkinsonian rats.
复制标题
NR2B 选择性 NMDA 受体拮抗剂 CP-101,606 可预防偏侧帕金森病大鼠左旋多巴诱导的运动反应改变。
DOI：
10.1016/j.neuropharm.2004.03.011
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发表时间：
2004
影响因子：
4.7
通讯作者：
Oh,JD
中科院分区：
文献类型：
--
作者：
Wessell,RH;Ahmed,SM;Menniti,FS;Dunbar,GL;Chase,TN;Oh,JD
Sensitization of NMDA receptors containing the NR2B subunit has been increasingly associated with various forms of synaptic plasticity, including those implicated in the pathogenesis of extrapyramidal motor dysfunction. To determine whether activation of NR2B containing receptors contributes to the development and maintenance of levodopa-induced response changes in parkinsonian animals, we evaluated the effects of the selective NR2B antagonist CP-101,606 on these response alterations in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. Three weeks of twice-daily levodopa treatment decreased the duration of the rotational response to acute levodopa challenge. The response alteration was associated with an increase in GluR1 (S831) phosphorylation in medium spiny neurons of the dorsolateral striatum. Both the attenuated rotational response and augmented GluR1 phosphorylation were decreased by CP-101,606 treatment. These CP-101,606 effects were observed when the compound was administered either at the end of chronic levodopa treatment (ameliorative effect) or together with the twice-daily levodopa treatment for 3 weeks (preventive effect). Furthermore, concurrent administration of CP-101,606 with levodopa potentiated the ability of levodopa challenge to reverse the 6-OHDA lesion-induced contralateral forelimb movement deficit as measured in a drag test. These results suggest that activation of NR2B subunit containing NMDA receptors contributes to both the development and maintenance of levodopa-induced motor response alterations, through a mechanism that involves an increase in GluR1 phosphorylation in striatal spiny neurons.
