Borlongan C V, Sanberg P R
Department of Surgery, University of South Florida College of Medicine, Tampa 33612, USA.
J Neurosci. 1995 Jul;15(7 Pt 2):5372-8. doi: 10.1523/JNEUROSCI.15-07-05372.1995.
Parkinson's disease is characterized by a depletion of dopamine (DA) neurons in the nigrostriatal pathway. Stereotaxic injections of 6-hydroxydopamine (6-OHDA), a selective neurotoxin, into either the medial forebrain bundle or the substantia nigra result in a massive DA denervation of the nigrostriatal pathway. Following unilateral nigrostriatal DA depletion, hemiparkinsonian animals develop a stereotypical rotational behavior when challenged with DA agonists such as apomorphine. The drug-induced rotational behavior has been widely used as the behavioral index of hemiparkinsonian animals, but it has some limitations. Although asymmetries in the rotational behavior may indicate an imbalance of DA contents and release capacity in the bilateral nigrostriatal pathway, the behavior is a pharmacological reaction. Accordingly, the drug-induced rotation test is subject to sensitization effects. The present study proposes the elevated body swing test (EBST) as a measure of asymmetrical motor behavior of hemiparkinsonian animals in a drug-free state. The EBST simply involves elevating the animal by handling its tail and recording the frequency and direction of the swing behavior. Unilateral nigral 6-OHDA-lesioned rats exhibited significant biased swing activity with the direction contralateral to the lesioned side, corresponding to the direction of apomorphine-induced rotations. A 30 sec EBST was noted as the peak time for biased swing activity. At 7 d postlesion (the start of testing), and every week thereafter for a period of 2 months, a fairly stable biased swing activity level was observed. At 1 and 2 months postlesion, the same animals were also challenged with apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)
帕金森病的特征是黑质纹状体通路中的多巴胺(DA)神经元耗竭。向内侧前脑束或黑质立体定向注射选择性神经毒素6-羟基多巴胺(6-OHDA)会导致黑质纹状体通路大量去多巴胺神经支配。单侧黑质纹状体DA耗竭后,半帕金森病动物在受到阿扑吗啡等DA激动剂刺激时会出现典型的旋转行为。药物诱导的旋转行为已被广泛用作半帕金森病动物的行为指标,但它有一些局限性。尽管旋转行为的不对称可能表明双侧黑质纹状体通路中DA含量和释放能力的不平衡,但这种行为是一种药理反应。因此,药物诱导的旋转试验容易受到敏化作用的影响。本研究提出将抬高身体摆动试验(EBST)作为一种在无药物状态下测量半帕金森病动物不对称运动行为的方法。EBST简单地包括通过抓住动物的尾巴将其抬高,并记录摆动行为的频率和方向。单侧黑质6-OHDA损伤的大鼠表现出明显的偏向摆动活动,摆动方向与损伤侧相反,与阿扑吗啡诱导的旋转方向一致。30秒的EBST被认为是偏向摆动活动的峰值时间。在损伤后7天(测试开始时),以及此后的两个月内每周观察到相当稳定的偏向摆动活动水平。在损伤后1个月和2个月,对同一批动物也进行了阿扑吗啡刺激。(摘要截断于250字)