Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia.
Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia.
复制标题
转化啮齿类动物范式研究精神分裂症中与动机缺失和改变的奖励处理相关的行为背后的神经机制。
DOI：
10.1093/schbul/sbv093
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发表时间：
2015
影响因子：
6.6
通讯作者：
Markou,Athina
中科院分区：
文献类型：
--
作者：
Young,JaredW;Markou,Athina
长期以来，精神分裂症患者的动机缺失和奖励处理缺陷被认为是导致患者无法很好地融入社会的重要原因。对于这些症状没有有效的治疗方法，部分原因是人们对介导这些症状的神经机制知之甚少。在这里，我们提出了一种转化神经科学方法，可用于使用也可以在实验动物中进行的行为范式来评估与精神分裂症阴性症状相关的奖励/动机缺陷。通过设计和使用在啮齿类动物和人类中参数相似的客观实验室行为工具，可以研究与精神分裂症这些症状相关的行为背后的神经机制。我们描述了衡量啮齿类动物花费体力和认知努力来获得奖励的动机的任务，以及评估奖励学习和基于反馈的决策的概率学习任务。后一项任务是相关的，因为已证明表现缺陷与精神分裂症患者的阴性症状相关。这些任务利用操作技术来研究针对跨物种特定域的神经回路。因此，这些任务能够深入了解导致精神分裂症患者出现阴性症状相关行为的改变机制。这些发现将使针对精神分裂症中这些改变的神经机制和行为的靶向治疗的开发成为可能。
Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients’ inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia.