CSC, an adenosine A2A receptor antagonist and MAO B inhibitor, reverses behavior, monoamine neurotransmission, and amino acid alteration in the 6-OHDA-lesioned rats
CSC, an adenosine A2A receptor antagonist and MAO B inhibitor, reverses behavior, monoamine neurotransmission, and amino acid alteration in the 6-OHDA-lesioned rats
复制标题
DOI：
10.1016/j.brainres.2007.11.051
复制
发表时间：
2008-01-29
期刊：
影响因子：
2.9
通讯作者：
Viana, Glauce S. B.
中科院分区：
文献类型：
--
作者：
Aquiar, Lissiana My.;Macedo, Danielle S.;Viana, Glauce S. B.
本工作观察了A（2A）受体拮抗剂和单胺氧化酶（MAO）B抑制剂8-（-3-chlorostyryl）-caffeine（CSC）对6-羟基多巴胺（6-OHDA）损伤大鼠行为学和生化指标的影响。雄性Wistar大鼠（280 g）注射CSC（1和5 mg/kg，腹腔注射）单独或与L-DOPA（50 mg/kg+苄丝肼12.5 mg/kg）组合，在纹状体6-OHDA损伤后6天开始，并且在接下来的7天每天一次。在6-OHDA损伤后14天（和CSC或媒介物后24小时），记录净身体旋转/小时的数目（在阿扑吗啡攻击后），并且在第二天，处死动物。同侧纹状体用于单胺和氨基酸的HPLC测量或用于测定亚硝酸盐含量和脂质过氧化。结果表明，阿扑吗啡刺激后，由6-OHDA损伤诱导的身体旋转增加被CSC显著且剂量依赖性地逆转。此外，在6-OHDA损伤的大鼠中，降低的纹状体DA和代谢物水平在CSC治疗后被逆转，并且这些作用在与L-DOPA组合后被增强。用NE、5-HT和5-HIAA观察到类似的结果。虽然谷氨酸和GABA在6-OHDA损伤组中增加，但CSC单独或主要与L-DOPA组合逆转了这些改变。此外，CSC治疗6-OHDA损伤大鼠逆转了6-OHDA诱导的亚硝酸盐形成和脂质过氧化反应的增加。总之，CSC通过其作为A2 A拮抗剂和MAO-B抑制剂的双重作用逆转了在6-OHDA损伤大鼠中观察到的行为和生化改变，指出了其治疗PD的潜在益处。(c)2007 Elsevier B. V.保留所有权利。
The present work showed the effects of 8-(-3-chlorostyryl)-caffeine (CSC), an A(2A) receptors antagonist and MAO B inhibitor, on behavior and biochemical alterations in 6-OHDA-lesioned rats. Male Wistar rats (280 g) were injected with CSC (1 and 5 mg/kg, i.p.) alone or combined with L-DOPA (SO mg/kg+benserazide 12.5 mg/kg), starting 6 days after the striatal 6-OHDA lesions, and once daily for the next 7 days. Fourteen days after the 6-OHDA lesion (and 24 h after CSC or vehicle), the number of net body rotations/h (after the apomorphine challenge) was recorded and, at the next day, animals were sacrificed. The ipsilateral striatum was used for HPLC measurements of monoamines and amino acids or for determination of nitrite contents and lipid peroxidation. Results showed that the increase in body rotation, induced by the 6-OHDA lesion, after the apomorphine challenge, was significantly and dose-dependently reversed by CSC. Furthermore, the decreased striatal levels of DA and metabolites, in the 6-OHDA-lesioned rats, were reversed after CSC treatment, and these effects were potentiated after the combination with L-DOPA. Similar results were observed with NE, 5-HT and 5-HIAA. While glutamate and GABA were increased in the 6-OHDA-lesioned group, CSC alone or mainly combined with L-DOPA reversed these alterations. In addition, the CSC treatment of 6-OHDA-lesioned rats reversed the increased nitrite formation and lipid peroxidation induced by 6-OHDA. In conclusion, CSC by means of its dual action as A2A antagonist and MAO-B inhibitor reversed behavior and biochemical alterations, observed in the 6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of PD. (c) 2007 Elsevier B.V. All rights reserved.