Department of Psychology, University of Memphis, 400 Innovation Drive, Memphis, TN, 38112, USA.
Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 55 N Lake Ave, Worcester, MA, 01655, USA.
Psychopharmacology (Berl). 2021 Apr;238(4):991-1004. doi: 10.1007/s00213-020-05745-z. Epub 2021 Jan 7.
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.
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.
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.
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.
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.
最优决策需要评估多个受到不同成本影响的奖励,例如高努力要求或高失败风险。神经递质多巴胺对于这些成本效益分析至关重要,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作用超出了传统啮齿动物经济决策范式的范围。
我们开发了努力与概率经济冲突任务(EvP),以在大鼠中模拟多模态经济决策。该任务测量了两种奖励之间的选择,这两种奖励的大小相同,但与高努力要求或奖励缺失的风险相关。然后,我们测试了系统可卡因和 D1/D2 阻断或激活对高努力和高风险替代方案之间偏好的调节作用。
在 EvP 中,两种大小相等的强化物与以下两种情况之一相关联:(1)整个会议期间逐渐增加的努力要求(1、5、10 和 20 个压杆按压),或(2)奖励获得的低概率(25%的概率选择)。关键是,每个选择的强化物是可比的(一个药丸),这消除了大小辨别对决策过程的影响。在确定任务后,在进行 EvP 之前,给予多巴胺转运体阻断剂可卡因和 D1/D2 拮抗剂和激动剂。
当任何一个选项变得更加昂贵时,对努力或概率选择的偏好都会转移,并且这种偏好在受试者之间高度可变且随时间稳定。可卡因、D1 激活和 D2 阻断仅产生有限的、剂量依赖性的选择偏好转变,取决于高或低努力条件。相比之下,多个剂量的 D2 激活会引起从费力到冒险的强烈选择转变,即使在明显不利的情况下也是如此。
EvP 清楚地表明,大鼠可以评估与可比大小的奖励相关的不同努力或风险成本,并随着成本的增加而转移对任何一个选项的偏好。这种偏好与 D2 受体的操纵比 D1 受体的操纵更为紧密相关,这表明 D2 样受体可能是一种治疗药物,可用于治疗对冒险的适应不良偏见而不是努力。