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帕金森病冲动-强迫行为的啮齿类动物模型:我们已经走了多远?

Rodent models of impulsive-compulsive behaviors in Parkinson's disease: How far have we reached?

机构信息

Basal Ganglia Pathophysiology, Dept. Exp. Med. Science, Lund University, Lund, Sweden.

Basal Ganglia Pathophysiology, Dept. Exp. Med. Science, Lund University, Lund, Sweden.

出版信息

Neurobiol Dis. 2015 Oct;82:561-573. doi: 10.1016/j.nbd.2015.08.026. Epub 2015 Aug 30.

DOI:10.1016/j.nbd.2015.08.026
PMID:26325219
Abstract

There is increasing awareness that the medications used to treat the motor symptoms of Parkinson's disease (PD) contribute to the development of behavioral addictions, which have been clinically defined as impulsive-compulsive behaviors (ICBs). These features include pathological gambling, compulsive sexual behavior, binge eating, compulsive shopping, excessive hobbyism or punding, and the excessive use of dopaminergic medication. ICBs frequently have devastating effects on the social and occupational function of the affected individuals as well as their families. Although ICBs are an important clinical problem in PD, the number of studies in which these symptoms have been modeled in rodents is still limited. This may depend on uncertainties regarding, on one hand, the pathophysiology of these behaviors and, on the other hand, the experimental paradigms with which similar features can be induced in rodents. To help compose these uncertainties, we will here review the characteristics of ICBs in PD patients and then describe behavioral methods to approximate them in rodents. We will discuss both the challenges and the possibilities of applying these methods to animals with PD-like lesions, and review the recent progress made to this end. We will finally highlight important questions deserving further investigation. Rodent models having both face validity and construct validity to parkinsonian ICBs will be essential to further pathophysiological and therapeutic studies into this important area.

摘要

人们越来越意识到,用于治疗帕金森病(PD)运动症状的药物会导致行为成瘾的发展,这些成瘾已在临床上定义为冲动-强迫行为(ICB)。这些特征包括病态赌博、强迫性行为、暴食、强迫性购物、过度癖好或强迫性刻板行为以及多巴胺能药物的过度使用。ICB 经常对受影响个体及其家人的社会和职业功能产生毁灭性影响。尽管 ICB 是 PD 中的一个重要临床问题,但在啮齿动物中对这些症状进行建模的研究数量仍然有限。这可能取决于以下两个方面的不确定性:一方面是这些行为的病理生理学,另一方面是可以在啮齿动物中诱导类似特征的实验范式。为了帮助解决这些不确定性,我们将在这里回顾 PD 患者中 ICB 的特征,然后描述在啮齿动物中近似这些特征的行为方法。我们将讨论在具有 PD 样病变的动物中应用这些方法的挑战和可能性,并回顾为此目的取得的最新进展。最后,我们将强调值得进一步研究的重要问题。具有帕金森病冲动-强迫行为的表面有效性和结构有效性的啮齿动物模型对于进一步研究这一重要领域的病理生理学和治疗学至关重要。

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