Jenni Nicole L, Li Yi Tao, Floresco Stan B
Department of Psychology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Neuropsychopharmacology. 2021 Jun;46(7):1240-1251. doi: 10.1038/s41386-020-00931-1. Epub 2021 Jan 15.
Efficient decision-making involves weighing the costs and benefits associated with different actions and outcomes to maximize long-term utility. The medial orbitofrontal cortex (mOFC) has been implicated in guiding choice in situations involving reward uncertainty, as inactivation in rats alters choice involving probabilistic rewards. The mOFC receives considerable dopaminergic input, yet how dopamine (DA) modulates mOFC function has been virtually unexplored. Here, we assessed how mOFC D and D receptors modulate two forms of reward seeking mediated by this region, probabilistic reversal learning and probabilistic discounting. Separate groups of well-trained rats received intra-mOFC microinfusions of selective D or D antagonists or agonists prior to task performance. mOFC D and D blockade had opposing effects on performance during probabilistic reversal learning and probabilistic discounting. D blockade impaired, while D blockade increased the number of reversals completed, both mediated by changes in errors and negative feedback sensitivity apparent during the initial discrimination of the task, which suggests changes in probabilistic reinforcement learning rather than flexibility. Similarly, D blockade reduced, while D blockade increased preference for larger/risky rewards. Excess D stimulation had no effect on either task, while excessive D stimulation impaired probabilistic reversal performance, and reduced both profitable risky choice and overall task engagement. These findings highlight a previously uncharacterized role for mOFC DA, showing that D and D receptors play dissociable and opposing roles in different forms of reward-related action selection. Elucidating how DA biases behavior in these situations will expand our understanding of the mechanisms regulating optimal and aberrant decision-making.
高效的决策涉及权衡与不同行动和结果相关的成本和收益，以实现长期效用最大化。内侧眶额皮质（mOFC）在涉及奖励不确定性的情境中指导选择，因为大鼠体内该区域失活会改变涉及概率性奖励的选择。mOFC接受大量多巴胺能输入，但多巴胺（DA）如何调节mOFC功能实际上尚未得到探索。在这里，我们评估了mOFC的D和D受体如何调节由该区域介导的两种奖励寻求形式，概率性反转学习和概率性折扣。在任务执行前，将经过良好训练的大鼠分为不同组，分别向mOFC内微量注射选择性D或D拮抗剂或激动剂。mOFC的D和D阻断在概率性反转学习和概率性折扣过程中对行为表现有相反的影响。D阻断会损害表现，而D阻断会增加完成的反转次数，这两者都是由任务初始辨别过程中明显的错误变化和负反馈敏感性介导的，这表明概率性强化学习发生了变化，而非灵活性发生了变化。同样，D阻断会降低，而D阻断会增加对更大/有风险奖励的偏好。过量的D刺激对任何一项任务都没有影响，而过量的D刺激会损害概率性反转表现，并减少有利可图的风险选择和整体任务参与度。这些发现突出了mOFC中DA以前未被描述的作用，表明D和D受体在不同形式的奖励相关行动选择中发挥着可分离的相反作用。阐明DA在这些情况下如何影响行为，将扩展我们对调节最佳和异常决策机制的理解。
