Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

摘要

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.