Cellular and behavioral effects of 5-HT1A receptor agonist 8-OH-DPAT in a rat model of levodopa-induced motor complications
Cellular and behavioral effects of 5-HT1A receptor agonist 8-OH-DPAT in a rat model of levodopa-induced motor complications
复制标题
DOI：
10.1016/j.brainres.2006.10.020
复制
发表时间：
2007-01-05
期刊：
影响因子：
2.9
通讯作者：
Liu, Zhenguo
中科院分区：
文献类型：
--
作者：
Ba, Maowen;Kong, Min;Liu, Zhenguo
刺激5-HT1a自身受体可以减弱长期使用左旋多巴后细胞外多巴胺水平的超生理波动，可能有助于运动并发症的治疗和预防。本研究的目的是观察5-HT1a受体激动剂8-OH-DPAT对左旋多巴诱发运动并发症大鼠的细胞和行为的影响。进行了两组实验。首先，动物给予左旋多巴(50 mg/kg+苯丝肼12.5 mg/kg，每日两次)，腹腔注射(Ip)。已经22天了。在第23天，动物注射8-OH-DPAT(1 mg/kg，ip)。或8-OH-DPAT+Way-100635(0.1mg.kg，ip)或赋形剂，每次剂量左旋多巴。在第二组中，动物接受左旋多巴(so mg/kg，i.p)治疗。外加8-羟基-DPAT(1 mg/kg，i.p.)或左旋多巴(50 mg/kg，ip)外加车辆，每日两次，连续22天。我们的研究表明，8-OH-DPAT与左旋多巴合用既延长了运动反应的持续时间，又减少了峰转。8-OH-DPAT加左旋多巴也减少了左旋多巴治疗失败的频率。联合应用5-HT1a受体拮抗剂Way-100635和8-OH-DPAT可消除8-OH-DPAT对运动并发症的影响，表明所观察到的8-OH-DPAT反应可能是通过5-HT1a自身受体介导的。此外，8-OH-DPAT联合左旋多巴显著降低GluR1丝氨酸845位的过度磷酸化，这与左旋多巴诱导的运动并发症密切相关。(C)2006爱思唯尔B.V.保留所有权利。
5-HT1A autoreceptor stimulation can act to attenuate supraphysiological swings in extracellular dopamine levels following long-term levodopa treatment and may be useful in the treatment and prevention of the motor complications. The purpose of this study was to investigate cellular and behavioral effects of 5-HT1A receptor agonist 8-OH-DPAT in a rat model of levodopa-induced motor complications. Two sets of experiments were performed. First, animals were treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg, twice daily), intraperitoneally (i.p.) for 22 days. On day 23, animals received either 8-OH-DPAT (1 mg/kg, i.p.) or 8-OH-DPAT plus WAY-100635 (0.1 mg/kg, i.p) or vehicle with each levodopa dose. In the second set, animals were treated either with levodopa (SO mg/kg, i.p.) plus 8-OH-DPAT (1 mg/kg, i.p.) or levodopa (50 mg/kg, i.p.) plus vehicle, administered twice daily for 22 consecutive days. our study showed that 8-OH-DPAT plus levodopa both prolonged the duration of the motor response and reduced peak turning. 8-OH-DPAT plus levodopa also decreased the frequency of failures to levodopa. Co-administration of WAY-100635, a 5-HT1A receptor antagonist, with 8-OH-DPAT eliminated the effect of 8-OH-DPAT on motor complications indicating that the observed 8-OH-DPAT responses were probably mediated at the 5-HT1A autoreceptor. Moreover, 8-OH-DPAT plus levodopa significantly reduced hyperphosphorylation of GluR1 at serine 845, which was closely associated with levodopa-induced motor complications. (c) 2006 Elsevier B.V. All rights reserved.