Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson's Disease.
Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson's Disease.
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在帕金森病动物模型中，5-HT1A受体在维拉唑酮介导的左旋多巴诱导的运动障碍抑制和纹状体中棘神经元对皮质输入的反应性增加中的作用
DOI：
10.3390/molecules26195790
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发表时间：
2021-09-24
期刊：
影响因子：
--
通讯作者：
West AR
中科院分区：
文献类型：
--
作者：
Altwal F;Padovan-Neto FE;Ritger A;Steiner H;West AR
左旋多巴治疗帕金森病（PD）是有限的，由于新兴的左旋多巴诱导的运动障碍。研究发现，多巴胺能（5-HT）末梢的异常多巴胺释放导致了这种运动障碍。选择性5-羟色胺再摄取抑制剂（SSRIs）或5-HT受体（5-HTr）激动剂可调节5-HT活性并减轻运动障碍，但它们通常也使L-DOPA的抗帕金森病功效丧失。我们研究了维拉唑酮，一种新型的多模式5-HT药物与SSRI和5-HTr 1A部分激动剂的特性，其潜力，以减少运动障碍，而不干扰的促动力作用的左旋多巴，和潜在的机制。我们评估了维拉唑酮对左旋多巴诱导的运动障碍（异常不自主运动，AIM）和异常反应的纹状体中型棘神经元（MSNs）的驱动器在体内单单位细胞外记录测量，在6-OHDA大鼠模型的PD。维拉唑酮（10 mg/kg）抑制L-DOPA（5 mg/kg）诱导的AIM的所有亚型（轴向、肢体、口舌）和MSN对皮质刺激反应性的增加（更短的尖峰起始潜伏期）。维拉唑酮的抗运动障碍作用和MSN兴奋性的逆转均被5-HTr 1A拮抗剂WAY-100635抑制，表明5-HTr 1A在这些维拉唑酮作用中起关键作用。我们的研究结果表明，维拉唑酮可作为一种辅助治疗，减少运动障碍的PD患者。
L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia. Research has identified abnormal dopamine release from serotonergic (5-HT) terminals contributing to this dyskinesia. Selective serotonin reuptake inhibitors (SSRIs) or 5-HT receptor (5-HTr) agonists can regulate 5-HT activity and attenuate dyskinesia, but they often also produce a loss of the antiparkinsonian efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr1A partial agonist properties, for its potential to reduce dyskinesia without interfering with the prokinetic effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia (abnormal involuntary movements, AIMs) and aberrant responsiveness to corticostriatal drive in striatal medium spiny neurons (MSNs) measured with in vivo single-unit extracellular recordings, in the 6-OHDA rat model of PD. Vilazodone (10 mg/kg) suppressed all subtypes (axial, limb, orolingual) of AIMs induced by L-DOPA (5 mg/kg) and the increase in MSN responsiveness to cortical stimulation (shorter spike onset latency). Both the antidyskinetic effects and reversal in MSN excitability by vilazodone were inhibited by the 5-HTr1A antagonist WAY-100635, demonstrating a critical role for 5-HTr1A in these vilazodone actions. Our results indicate that vilazodone may serve as an adjunct therapeutic for reducing dyskinesia in patients with PD.
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影响因子：
6
作者：
Altwal F;Moon C;West AR;Steiner H
通讯作者：
Steiner H
长时间选择性5-羟色胺再摄取抑制对Hemi-Parkinsonian大鼠L- dopa诱导的运动障碍的发育和表达的影响。
影响因子：
4.7
作者：
Conti MM;Ostock CY;Lindenbach D;Goldenberg AA;Kampton E;Dell'isola R;Katzman AC;Bishop C
通讯作者：
Bishop C
影响因子：
8.6
作者：
Bezard, Erwan;Tronci, Elisabetta;Carta, Manolo
通讯作者：
Carta, Manolo
DOI：
10.1016/b978-0-12-802206-1.00043-x
发表时间：
2016-01-01
期刊：
HANDBOOK OF BASAL GANGLIA STRUCTURE AND FUNCTION, 2ND EDITION
影响因子：
--
作者：
Cenci, M. A.
通讯作者：
Cenci, M. A.
影响因子：
25
作者：
Calabresi, Paolo;Pisani, Antonio;Picconi, Barbara
通讯作者：
Picconi, Barbara