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急性左旋多巴预处理对帕金森病大鼠模型中阿扑吗啡诱导的旋转行为的影响。

Effect of acute L-Dopa pretreatment on apomorphine-induced rotational behavior in a rat model of Parkinson's disease.

作者信息

Mandel R J

机构信息

Department of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, 32610-0244, USA.

出版信息

Exp Neurol. 2000 Jan;161(1):212-9. doi: 10.1006/exnr.1999.7245.

Abstract

Currently, reduction of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) lesioned rat is the most utilized drug-induced paradigm for assessing functional efficacy in a rat model of Parkinson's disease (PD). Any clinically predictive animal model of PD should include a positive response to l-dopa, the standard pharmacotherapy for PD. However, the acute interaction between L-dopa and apomorphine has never been studied to determine if L-dopa pretreatment could reduce apomorphine-induced rotational behavior in a 6-OHDA lesioned rat. The present study was designed to explore whether, indeed, pretreatment with subrotational doses of L-dopa could inhibit apomorphine-induced rotations. The data indicate that L-dopa significantly reduced apomorphine-induced rotational behavior only at one dose (5.0 mg/kg) for 12 min. Based on these and other data, it is concluded that although the apomorphine-induced rotational paradigm may continue to be utilized as one additional indicator of efficacy in the 6-OHDA rat model of PD, it is not in itself a completely valid functional assay.

摘要

目前,在6-羟基多巴胺(6-OHDA)损伤的大鼠中,减少阿扑吗啡诱导的旋转行为是评估帕金森病(PD)大鼠模型功能疗效时最常用的药物诱导范式。任何具有临床预测性的PD动物模型都应包括对左旋多巴(治疗PD的标准药物疗法)产生阳性反应。然而,左旋多巴与阿扑吗啡之间的急性相互作用从未被研究过,以确定左旋多巴预处理是否能减少6-OHDA损伤大鼠中阿扑吗啡诱导的旋转行为。本研究旨在探讨亚旋转剂量的左旋多巴预处理是否确实能抑制阿扑吗啡诱导的旋转。数据表明,左旋多巴仅在一个剂量(5.0mg/kg)下持续12分钟时能显著降低阿扑吗啡诱导的旋转行为。基于这些及其他数据,得出的结论是,尽管阿扑吗啡诱导的旋转范式可能会继续被用作6-OHDA PD大鼠模型中疗效的另一指标,但它本身并不是一个完全有效的功能检测方法。

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