Serotonin 1A receptor agonist modulation of motor deficits and cortical oscillations by NMDA receptor interaction in parkinsonian rats
Serotonin 1A receptor agonist modulation of motor deficits and cortical oscillations by NMDA receptor interaction in parkinsonian rats
复制标题
5-羟色胺 1A 受体激动剂通过 NMDA 受体相互作用调节帕金森病大鼠的运动缺陷和皮质振荡
DOI：
10.1016/j.neuropharm.2021.108881
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发表时间：
2021-11-17
影响因子：
4.7
通讯作者：
Wang, Xiaomin
中科院分区：
文献类型：
--
作者：
Jiang, Xinxin;Liang, Peirong;Wang, Xiaomin
虽然5-HT 1A受体激动剂被广泛用作减轻帕金森病（PD）运动障碍的辅助药物，但很少有研究关注5-HT 1A受体激动剂对PD运动症状的影响及其机制。使用单侧6-羟基多巴胺（6-OHDA）损伤的大鼠，并在这些大鼠的运动皮层中植入电极。因此，本研究评价了5-HT 1A受体激动剂8-OH-DPAT对运动行为和振荡活动的影响。此外，8-OHDPAT与D2受体拮抗剂雷氯必利、NMDA受体拮抗剂MK-801或其激动剂Dcycloserine（DCS）联合给药。8-OH-DPAT给药显著改善6-OHDA损伤大鼠的自发活动和不对称前爪功能。同时，8-OH-DPAT确定了6-OHDA损伤大鼠运动皮层中异常高β振荡（25-40 Hz）的选择性调制，而不会诱导80 Hz左右的病理性微调γ。与8-OH-DPAT不同，左旋多巴治疗对运动性能和高β和γ振荡的差异调节产生了长期的改善。多巴胺D2受体拮抗剂对8-OH-DPAT介导的运动行为和β振荡无影响。相比之下，阈下NMDA受体拮抗剂MK-801明显提高了8-OH-DPAT介导的运动行为，而NMDA受体激动剂DCS部分减轻了8-OH-DPAT介导的症状。这项研究表明，5-HT 1A受体激动剂8-OH-DPAT改善运动活动和调节帕金森病大鼠运动皮层的振荡。与L-多巴不同，8-OH-DPAT给药通过多巴胺能途径而不是多巴胺能途径改善PD的运动症状。
Although serotonin 1A (5-HT1A) receptor agonists are widely used as the additive compound to reduce L-dopainduced dyskinesia in Parkinson's disease (PD), few studies focused on the effect and mechanism of 5-HT1A receptor agonist on the motor symptoms of PD. Unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats were used and implantation of electrodes was performed in the motor cortex of these rats. So the effect of 5-HT1A receptor agonist 8-OH-DPAT on motor behaviors and oscillatory activities were evaluated. In addition, 8-OHDPAT combined with D2 receptor antagonist raclopride, NMDA receptor antagonist MK-801, or its agonist Dcycloserine (DCS) were co-administrated. 8-OH-DPAT administration significantly improved spontaneous locomotor activity and asymmetric forepaw function in 6-OHDA-lesioned rats. Meanwhile, 8-OH-DPAT identified selective modulation of the abnormal high beta oscillations (25-40 Hz) in the motor cortex of 6-OHDA-lesioned rats, without inducing pathological finely tuned gamma around 80 Hz. Different from 8-OH-DPAT, L-dopa treatment produced a prolonged improvement on motor performances and differential regulation of high beta and gamma oscillations. However, dopamine D2 receptor antagonist had no influence on the 8-OH-DPAT-mediated-motor behaviors and beta oscillations in 6-OHDA-lesioned rats. In contrast, subthreshold NMDA receptor antagonist MK-801 obviously elevated the 8-OH-DPAT-mediated-motor behaviors, while NMDA receptor agonist DCS partially impaired the 8-OH-DPAT-mediated symptoms in 6-OHDA-lesioned rats. This study suggests that 5HT1A receptor agonist 8-OH-DPAT improves motor activity and modulates the oscillations in the motor cortex of parkinsonian rats. Different from L-dopa, 8-OH-DPAT administration ameliorates motor symptoms of PD through glutamatergic rather than the dopaminergic pathway.