Rodent studies on effort-related responding provide a tool to analyze basal aspects of motivation and to model psychiatric motivational dysfunctions reflecting low exertion of effort or reduced behavioral activation. It turned out that dopamine (DA) signaling in brain areas such as nucleus accumbens are essential in regulating effort-related motivational function and could play a major role in motivational dysfunction in psychiatric disorders. Recent rodent studies revealed that the medial orbitofrontal cortex (mOFC) is another key component of the neural circuitry regulating effort-related motivational function. The mOFC receives prominent DA input, however, the behavioral role of mOFC DA signaling is unknown. Here, we investigated whether DA signaling in the mOFC supports effort-related responding in rats. Results demonstrate that an intra-mOFC D1 receptor blockade markedly reduced effort-related responding in a progressive ratio task. Notably, the magnitude of this effect was comparable to the one caused by a systemic DA depletion induced by the VMAT-2 inhibitor tetrabenazine or by a satiety-induced motivational downshift. Collectively, our data show for the first time that D1 receptor activity in the mOFC plays a critical role in high effort responding. These results support findings in humans pointing to a role of the mOFC in effort-related responding. It is well known that the mOFC becomes dysfunctional in depression and schizophrenia. Our data point to the possibility that reduced mOFC DA activity could contribute to effort-related motivational symptoms in these disorders and support the notion that the DA system may be a drug target to treat effort-related motivational symptoms.

中文翻译：

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内侧眶额叶皮层中的多巴胺 D1 受体支持大鼠的努力相关反应

啮齿类动物对努力相关反应的研究提供了一种工具来分析动机的基本方面，并模拟反映低努力或行为激活减少的精神动机功能障碍。事实证明，伏隔核等大脑区域中的多巴胺 (DA) 信号传导对于调节与努力相关的动机功能至关重要，并且可能在精神疾病的动机功能障碍中发挥重要作用。最近的啮齿动物研究表明，内侧眶额皮质 (mOFC) 是调节与努力相关的动机功能的神经回路的另一个关键组成部分。mOFC 接收突出的 DA 输入，但是，mOFC DA 信号的行为作用尚不清楚。在这里，我们调查了 mOFC 中的 DA 信号是否支持大鼠的努力相关反应。结果表明，mOFC 内 D1 受体阻断显着减少了渐进式比率任务中与努力相关的反应。值得注意的是，这种影响的程度与 VMAT-2 抑制剂丁苯那嗪引起的系统性 DA 耗竭或饱腹感引起的动机下降引起的影响相当。总的来说，我们的数据首次表明 mOFC 中的 D1 受体活性在高努力响应中起着关键作用。这些结果支持人类的发现，指出 mOFC 在与努力相关的反应中的作用。众所周知，mOFC 在抑郁症和精神分裂症中变得功能失调。