Department of Pharmacology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Pharmacol Rep. 2011;63(4):908-14. doi: 10.1016/s1734-1140(11)70606-5.
In Parkinson's disease (PD), prolonged exposure to L-3,4-dihydroxyphenylalanine (L-DOPA) results in motor fluctuations, such as the on-off phenomenon, and L-DOPA-induced dyskinesia. Previously, we found that activation of 5-HT(1A) in the substantia nigra pars compacta (SNc) decreased catalepsy in parkinsonian rats. In the current investigation, we attempted to evaluate the effect of buspirone on the anti-cataleptic effect of L-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned male Wistar rats. Catalepsy was induced by the unilateral infusion of 6-OHDA (8 μg/2 μl/rat) into the central region of the SNc. After a 3-week recovery period, rats received L-DOPA intraperitoneally (ip; 15 mg/kg) twice daily for 20 days, and the anti-cataleptic effect of L-DOPA was assessed by the bar test at days 5, 10, 15 and 20. The results showed that L-DOPA had an anti-cataleptic effect only until day 15, and its effect was abolished on day 20. On day 21, these rats were co-treated with three different doses of buspirone (0.1, 0.5 and 2.5 mg/kg, ip) and L-DOPA (15 mg/kg, ip). At a dose of 0.5 mg/kg, buspirone improved the anti-cataleptic effect of L-DOPA. Furthermore, the effect of buspirone (0.5 mg/kg, ip) on the anti-cataleptic effect of L-DOPA (15 mg/kg, ip) was reversed by 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine hydrobromide (NAN-190; 0.5 mg/kg, ip), a 5-HT(1A) receptor antagonist. From these results, it may be concluded that buspirone improves the anti-cataleptic effect of L-DOPA in a 6-OHDA-induced animal model of PD through the activation of 5-HT(1A) receptors. In this regard, further investigations should be undertaken to clarify the exact mechanism of the interaction between 5-HT(1A) and dopaminergic neurons.
在帕金森病（PD）中，长时间暴露于 L-3,4-二羟基苯丙氨酸（L-DOPA）会导致运动波动，如开-关现象和 L-DOPA 诱导的运动障碍。先前，我们发现 5-HT（1A）在黑质致密部（SNc）中的激活可降低帕金森病大鼠的僵住症。在当前的研究中，我们试图评估丁螺环酮对 6-羟多巴胺（6-OHDA）损伤的雄性 Wistar 大鼠中 L-DOPA 抗僵住作用的影响。通过将 6-OHDA（8 μg/2 μl/rat）单侧输注到 SNc 的中央区域来诱导僵住症。经过 3 周的恢复期后，大鼠每天腹膜内（ip）给予 L-DOPA 15mg/kg，连续 20 天，并在第 5、10、15 和 20 天通过棒测试评估 L-DOPA 的抗僵住作用。结果表明，L-DOPA 仅在第 15 天具有抗僵住作用，而在第 20 天其作用被消除。在第 21 天，这些大鼠同时接受三种不同剂量的丁螺环酮（0.1、0.5 和 2.5mg/kg，ip）和 L-DOPA（15mg/kg，ip）治疗。在 0.5mg/kg 的剂量下，丁螺环酮改善了 L-DOPA 的抗僵住作用。此外，5-HT（1A）受体拮抗剂 1-（2-甲氧基苯基）-4-（4-邻苯二甲酰亚氨基丁基）哌嗪氢溴酸盐（NAN-190；0.5mg/kg，ip）可逆转丁螺环酮（0.5mg/kg，ip）对 L-DOPA（15mg/kg，ip）抗僵住作用。从这些结果可以得出结论，丁螺环酮通过激活 5-HT（1A）受体改善了 6-OHDA 诱导的 PD 动物模型中 L-DOPA 的抗僵住作用。在这方面，应进行进一步的研究以阐明 5-HT（1A）和多巴胺能神经元之间相互作用的确切机制。
