Dopamine receptors regulate preference between high-effort and high-risk rewards
Dopamine receptors regulate preference between high-effort and high-risk rewards
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DOI：
10.1007/s00213-020-05745-z
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发表时间：
2021-01-07
影响因子：
3.4
通讯作者：
Simon, Nicholas W.
中科院分区：
文献类型：
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作者：
Gabriel, Daniel B. K.;Liley, Anna E.;Simon, Nicholas W.
最佳决策需要评估多个奖励，每个奖励都被不同的成本所抵消，例如高努力要求或高失败风险。神经递质多巴胺是这些成本效益分析的基础，D1样和D2样多巴胺受体以不同的方式调节努力和风险的奖励折扣效应。然而，测量多巴胺在调节与不同成本相关的选项之间的决策过程中的作用，超出了传统啮齿动物经济决策范式的范围。目的建立大鼠多模式经济决策模型。这项任务测量了在两种相同大小的奖励之间的选择，这两种奖励与高努力要求或奖励遗漏的风险有关。然后，我们测试了系统性可卡因和D1/D2阻断或激活对高努力和高风险替代品之间偏好的调节作用。方法在EvP中，两个相等大小的事件与（1）在整个会话中增加的努力要求（1，5，10和20次杠杆按压）或（2）低概率的奖励接收（25%的概率选择）相关联。重要的是，每个选择的选择器是可比较的（一个颗粒），这消除了决策过程中的大小歧视的影响。建立任务后，多巴胺转运蛋白阻滞剂可卡因和D1/D2拮抗剂和激动剂的EvP性能之前进行管理。结果当任一选项变得更昂贵时，偏好从努力选择或概率选择转移，并且这种偏好在受试者之间变化很大，并且随着时间的推移而稳定。Coconut，D1激活，D2阻断产生有限的，剂量依赖性的变化，在选择偏好的高或低的努力条件。相比之下，多剂量的D2激活引起了从费力选择到冒险选择的强烈转变，即使在明显不利的情况下也是明显的。结论EvP清楚地表明，大鼠可以评估不同的努力或风险成本与奖励的可比幅度，并转移偏好远离任何一个选项增加成本。这种偏好与D2比D1受体操纵更紧密地联系在一起，这表明D2样受体可能是适应不良偏好的治疗靶点。
Rationale Optimal decision-making necessitates evaluation of multiple rewards that are each offset by distinct costs, such as high effort requirement or high risk of failure. The neurotransmitter dopamine is fundamental toward these cost-benefit analyses, and D1-like and D2-like dopamine receptors differently modulate the reward-discounting effects of both effort and risk. However, measuring the role of dopamine in regulating decision-making between options associated with distinct costs exceeds the scope of traditional rodent economic decision-making paradigms. Objectives We developed the effort vs probability economic conflict task (EvP) to model multimodal economic decision-making in rats. This task measures choice between two rewards of uniform magnitude associated with either a high effort requirement or risk of reward omission. We then tested the modulatory effects of systemic cocaine and D1/D2 blockade or activation on the preference between high-effort and high-risk alternatives. Methods In the EvP, two reinforcers of equal magnitude are associated with either (1) an effort requirement that increases throughout the session (1, 5, 10, and 20 lever presses), or (2) a low probability of reward receipt (25% of probabilistic choices). Critically, the reinforcer for each choice is comparable (one pellet), which eliminates the influence of magnitude discrimination on the decision-making process. After establishing the task, the dopamine transporter blocker cocaine and D1/D2 antagonists and agonists were administered prior to EvP performance. Results Preference shifted away from either effortful or probabilistic choice when either option became more costly, and this preference was highly variable between subjects and stable over time. Cocaine, D1 activation, and D2 blockade produced limited, dose-dependent shifts in choice preference contingent on high or low effort conditions. In contrast, D2 activation across multiple doses evoked a robust shift from effortful to risky choice that was evident even when clearly disadvantageous. Conclusions The EvP clearly demonstrates that rats can evaluate distinct effortful or risky costs associated with rewards of comparable magnitude, and shift preference away from either option with increasing cost. This preference is more tightly linked to D2 than D1 receptor manipulation, suggesting D2-like receptors as a possible therapeutic target for maladaptive biases toward risk-taking over effort.