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理解快感缺失的啮齿动物模型。

Making Sense of Rodent Models of Anhedonia.

机构信息

Department of Molecular and Developmental Medicine, University of Siena.

出版信息

Int J Neuropsychopharmacol. 2018 Nov 1;21(11):1049-1065. doi: 10.1093/ijnp/pyy083.

Abstract

A markedly reduced interest or pleasure in activities previously considered pleasurable is a main symptom in mood disorder and psychosis and is often present in other psychiatric disorders and neurodegenerative diseases. This condition can be labeled as "anhedonia," although in its most rigorous connotation the term refers to the lost capacity to feel pleasure that is one aspect of the complex phenomenon of processing and responding to reward. The responses to rewarding stimuli are relatively easy to study in rodents, and the experimental conditions that consistently and persistently impair these responses are used to model anhedonia. To this end, long-term exposure to environmental aversive conditions is primarily used, and the resulting deficits in reward responses are often accompanied by other deficits that are mainly reminiscent of clinical depressive symptoms. The different components of impaired reward responses induced by environmental aversive events can be assessed by different tests or protocols that require different degrees of time allocation, technical resources, and equipment. Rodent models of anhedonia are valuable tools in the study of the neurobiological mechanisms underpinning impaired behavioral responses and in the screening and characterization of drugs that may reverse these behavioral deficits. In particular, the antianhedonic or promotivational effects are relevant features in the spectrum of activities of drugs used in mood disorders or psychosis. Thus, more than the model, it is the choice of tests that is crucial since it influences which facets of anhedonia will be detected and should be tuned to the purpose of the study.

摘要

对以前被认为愉快的活动明显失去兴趣或乐趣是情绪障碍和精神病的主要症状,并且经常存在于其他精神疾病和神经退行性疾病中。这种情况可以被标记为“快感缺失”,尽管在其最严格的含义中,该术语是指失去感受快乐的能力,这是处理和响应奖励的复杂现象的一个方面。对奖赏刺激的反应在啮齿动物中相对容易研究,并且一致且持续地损害这些反应的实验条件用于模拟快感缺失。为此,长期暴露于环境厌恶条件下主要用于此,并且对奖赏反应的这些缺陷通常伴随着其他缺陷,主要类似于临床抑郁症状。环境厌恶事件引起的受损奖赏反应的不同成分可以通过不同的测试或方案来评估,这些测试或方案需要不同程度的时间分配、技术资源和设备。快感缺失的啮齿动物模型是研究受损行为反应背后的神经生物学机制以及筛选和表征可能逆转这些行为缺陷的药物的有价值的工具。特别是,抗快感缺失或促进作用是用于情绪障碍或精神病的药物的活动谱中的相关特征。因此,与其说是模型,不如说是测试的选择至关重要,因为它会影响到快感缺失的哪些方面被检测到,并且应该根据研究的目的进行调整。

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