Deficits in goal-directed motivation represent a debilitating symptom for many patients with schizophrenia. Impairments in motivation can arise from deficits in processing information about effort and or value, disrupting effective cost-benefit decision making. We have previously shown that upregulated dopamine D2 receptor expression within the striatum (D2R-OE mice) decreases goal-directed motivation. Here, we determine the behavioral and neurochemical mechanisms behind this deficit. Female D2R-OE mice were tested in several behavioral paradigms including recently developed tasks that independently assess the impact of Value or Effort manipulations on cost-benefit decision making. In vivo microdialysis was used to measure extracellular dopamine in the striatum during behavior. In a value-based choice task, D2R-OE mice show normal sensitivity to changes in reward value and used reward value to guide their actions. In an effort-based choice task, D2R-OE mice evaluate the cost of increasing the number of responses greater relative to the effort cost of longer duration responses compared to controls. This shift away from choosing to repeatedly execute a response is accompanied by a dampening of extracellular dopamine in the striatum during goal-directed behavior. In the ventral striatum, extracellular dopamine level negatively correlates with response cost in controls, but this relationship is lost in D2R-OE mice. These results show that D2R signaling in the striatum, as observed in some patients with schizophrenia, alters the relationship between effort expenditure and extracellular dopamine. This dysregulation produces motivation deficits that are specific to effort but not value-based decision making, paralleling the effort-based motivational deficits observed in schizophrenia.

中文翻译：

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纹状体多巴胺D2受体调节工作量，但不调节基于价值的决策，并改变费用的多巴胺能编码。

目标导向动力不足对许多精神分裂症患者而言是一种使人衰弱的症状。动机障碍可能来自处理有关努力和/或价值的信息不足，从而破坏了有效的成本效益决策。我们以前已经表明，纹状体（D2R-OE小鼠）内多巴胺D2受体表达上调降低了目标导向的动机。在这里，我们确定此缺陷背后的行为和神经化学机制。在几种行为模式中对雌性D2R-OE小鼠进行了测试，包括最近开发的任务，这些任务独立地评估了“价值或精力”操作对成本效益决策的影响。体内微透析用于在行为期间测量纹状体中的细胞外多巴胺。在基于价值的选择任务中，D2R-OE小鼠对奖励价值的变化表现出正常的敏感性，并使用奖励价值来指导其行为。在基于工作量的选择任务中，与对照组相比，D2R-OE小鼠评估增加响应数的成本相对于更长持续时间的响应的工作成本更大。在选择定向行为的过程中，这种选择重复执行反应的转变伴随着纹状体中细胞外多巴胺的减弱。在腹侧纹状体中，细胞外多巴胺水平与对照组的反应成本呈负相关，但这种关系在D2R-OE小鼠中消失了。这些结果表明，如在某些精神分裂症患者中观察到的，纹状体中的D2R信号改变了精力消耗与细胞外多巴胺之间的关系。