Striatal 5-HT1A receptor stimulation reduces D1 receptor-induced dyskinesia and improves movement in the hemiparkinsonian rat.
Striatal 5-HT1A receptor stimulation reduces D1 receptor-induced dyskinesia and improves movement in the hemiparkinsonian rat.
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DOI：
10.1016/j.neuropharm.2008.08.031
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发表时间：
2008-12
影响因子：
4.7
通讯作者：
Bishop C
中科院分区：
文献类型：
--
作者：
Dupre KB;Eskow KL;Barnum CJ;Bishop C
越来越多的证据表明，5-羟色胺5-HT 1A受体（5-HT 1AR）激动剂通过自调节中缝纹状体神经元中L-DOPA衍生的多巴胺（DA）的异常释放来减少L-DOPA诱导的运动障碍。然而，最近的研究结果表明，5-HT 1AR刺激也修改D1受体（D1 R）介导的运动障碍和旋转，涉及以前未探索的中缝外机制。为了表征纹状体对这些效应的贡献，在纹状体微量输注5-HT 1AR激动剂±8-OH-DPAT和全身性D1 R激动剂SKF 81297治疗后，对内侧前脑束DA损伤的大鼠进行了异常不自主运动（AIM）和旋转测试。在有或没有全身SKF 81297的情况下，在全身或纹状体内±8-OH-DPAT后，测试具有多部位纹状体DA损伤的其他大鼠的运动残疾。在内侧前脑束损伤的大鼠中，纹状体输注±8-OH-DPAT剂量依赖性地减少AIM，而相反地增加旋转。在纹状体损伤的大鼠中，±8-OH-DPAT单独全身和纹状体内给药可最佳逆转运动障碍。总的来说，这些结果支持纹状体中5-HT 1AR和D1 R之间的重要功能相互作用，这对改善帕金森病的治疗具有重要意义。
Convergent evidence suggests that serotonin 5-HT1A receptor (5-HT1AR) agonists reduce L-DOPA-induced dyskinesia by auto-regulating aberrant release of L-DOPA-derived dopamine (DA) from raphestriatal neurons. However, recent findings indicate that 5-HT1AR stimulation also modifies D1 receptor (D1R)-mediated dyskinesia and rotations implicating a previously unexplored extra-raphe mechanism. In order to characterize the contribution of the striatum to these effects, rats with medial forebrain bundle DA lesions were tested for abnormal involuntary movements (AIMs) and rotations following striatal microinfusions of the 5-HT1AR agonist ±8-OH-DPAT and systemic D1R agonist treatment with SKF81297. Additional rats with multi-site striatal DA lesions were tested for motor disability following systemic or intrastriatal ±8-OH-DPAT with or without systemic SKF81297. In rats with medial forebrain bundle lesions, striatal infusions of ±8-OH-DPAT dose-dependently reduced AIMs while conversely increasing rotations. In rats with striatal lesions, ±8-OH-DPAT alone, both systemic and intrastriatal administration, optimally reversed motor disability. Collectively, these results support an important functional interaction between 5-HT1AR and D1R in the striatum with implications for the improved treatment of Parkinson’s disease.
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影响因子：
2.3
作者：
Antonelli, T;Fuxe, K;Ferraro, L
通讯作者：
Ferraro, L
影响因子：
2.9
作者：
Ba, Maowen;Kong, Min;Liu, Zhenguo
通讯作者：
Liu, Zhenguo
DOI：
10.1124/jpet.106.110429
发表时间：
2006-12-01
影响因子：
3.5
作者：
Iravani, Mahmoud M.;Tayarani-Binazir, Kayhan;Jenner, Peter
通讯作者：
Jenner, Peter
影响因子：
4.8
作者：
Fiorentini, C;Gardoni, F;Missale, C
通讯作者：
Missale, C
影响因子：
9.9
作者：
Bibbiani, F;Oh, JD;Chase, TN
通讯作者：
Chase, TN