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单侧多巴胺耗竭大鼠的药物诱导旋转强度与前肢或后肢运动表现的终点或定性指标无关。

Drug-induced rotation intensity in unilateral dopamine-depleted rats is not correlated with end point or qualitative measures of forelimb or hindlimb motor performance.

作者信息

Metz G A, Whishaw I Q

机构信息

Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, AB, Canada T1K 3M4.

出版信息

Neuroscience. 2002;111(2):325-36. doi: 10.1016/s0306-4522(02)00013-1.

Abstract

The pharmacological induction of rotational (circling) behavior is widely used to assess the effects of lesions to the dopaminergic system and the success of treatment strategies in rat models of Parkinson's disease. While the number of rotations under apomorphine, L-DOPA and amphetamine is related to the extent of dopamine depletion after unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system, the relationship of the intensity of rotational behavior to the degree of impairment in motor behavior is unclear. The present study examined this question by correlating rotational behavior and motor abilities in a rat analogue for Parkinson's disease produced by unilateral nigrostriatal bundle lesion with 6-hydroxydopamine. Ipsiversive and contraversive rotation was measured in the rats following systemic administration of low and high doses of apomorphine, the dopamine precursor L-DOPA, and amphetamine. The motor assessment included end point and qualitative measures of fore- and hindlimbs assessed in a skilled reaching task and a skilled ladder rung walking task. The intensity of drug-induced rotation did not correlate with the measures of motor performance. We conclude that independence of rotational behavior and motor performance argues that both the assessment of 6-hydroxydopamine behavioral deficits and potential treatments for the functional deficits require comprehensive assessment, including both measures of rotation and motor behavior.

摘要

旋转(转圈)行为的药理学诱导被广泛用于评估帕金森病大鼠模型中多巴胺能系统损伤的影响以及治疗策略的成效。虽然阿扑吗啡、左旋多巴和苯丙胺作用下的旋转次数与黑质纹状体多巴胺系统单侧6-羟基多巴胺损伤后多巴胺耗竭的程度相关,但旋转行为强度与运动行为受损程度之间的关系尚不清楚。本研究通过将单侧黑质纹状体束6-羟基多巴胺损伤所致帕金森病大鼠模型中的旋转行为与运动能力进行关联,来探讨这一问题。在大鼠全身给予低剂量和高剂量的阿扑吗啡、多巴胺前体左旋多巴以及苯丙胺后,测量其同侧旋转和对侧旋转。运动评估包括在熟练抓握任务和熟练爬梯行走任务中对前肢和后肢的终点和定性测量。药物诱导的旋转强度与运动表现指标不相关。我们得出结论,旋转行为和运动表现的独立性表明,对6-羟基多巴胺行为缺陷的评估以及对功能缺陷的潜在治疗都需要进行全面评估,包括旋转测量和运动行为测量。

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