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首页> 外文期刊>Brain research >The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold dose of l-dopa in unilaterally 6-OHDA-lesioned rats.
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The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold dose of l-dopa in unilaterally 6-OHDA-lesioned rats.

机译：新型腺苷A2a拮抗剂ST1535在单侧6-OHDA损伤的大鼠中增强阈值剂量的左旋多巴。

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摘要

Adenosine A2a antagonists can modulate dopamine-mediated motor behaviours, however, their ability to induce rotational behaviour in 6-hydroxydopamine (6-OHDA)-lesioned rats and to potentiate the effects of l-dopa differs. We now report on the effects of the novel A2a antagonist ST1535 on rotational responses in this model. When administered alone, ST1535 (2.5-40 mg/kg po) enhanced exploratory behaviour and produced a dose-related increase in ipsilateral rotation in rats with a unilateral 6-OHDA lesion of the nigro-striatal pathway. Administration of ST1535 (40 mg/kg po) in combination with a high dose of l-dopa (12 mg/kg ip) caused marked contraversive rotation but did not alter the rotational response produced by l-dopa alone. In contrast, when administered in combination with l-dopa (7 mg/kg ip) that alone produced a submaximal circling response, ST1535 enhanced the intensity and duration of rotation. These results suggest that ST1535 is able to alter dopamine-mediated behaviour when given alone and to potentiate the effects of submaximal doses of l-dopa. ST1535 may be useful in the treatment of Parkinson's disease and effective in reducing the use of l-dopa.
机译：腺苷A2a拮抗剂可以调节多巴胺介导的运动行为，但是，它们在6-羟基多巴胺（6-OHDA）损伤的大鼠中诱导旋转行为并增强l-多巴的作用的能力不同。现在，我们在该模型中报告新型A2a拮抗剂ST1535对旋转反应的影响。当单独给药时，ST1535（2.5-40 mg / kg口服）可增强探索性行为，并在黑质纹状体途径的单侧6-OHDA损伤大鼠的同侧旋转中产生剂量相关的增加。 ST1535（40 mg / kg口服）与高剂量的l-dopa（12 mg / kg ip ip）组合给药可引起明显的自发旋转，但不会改变单独使用l-dopa产生的旋转反应。相反，当与单独产生次最大循环反应的左旋多巴（7 mg / kg ip）联合给药时，ST1535增强了旋转的强度和持续时间。这些结果表明，当单独给予时，ST1535能够改变多巴胺介导的行为，并增强亚最大剂量的左旋多巴的作用。 ST1535可用于治疗帕金森氏病，并有效减少左旋多巴的使用。

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