Dopamine D1/D2 Receptor Activity in the Nucleus Accumbens Core But Not in the Nucleus Accumbens Shell and Orbitofrontal Cortex Modulates Risk-Based Decision Making
Dopamine D1/D2 Receptor Activity in the Nucleus Accumbens Core But Not in the Nucleus Accumbens Shell and Orbitofrontal Cortex Modulates Risk-Based Decision Making
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DOI：
10.1093/ijnp/pyv043
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发表时间：
2015-09-01
影响因子：
4.8
通讯作者：
Hauber, Wolfgang
中科院分区：
文献类型：
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作者：
Mai, Bettina;Sommer, Susanne;Hauber, Wolfgang
背景：众所周知，大脑多巴胺（DA）信号支持基于风险的决策；然而，中脑DA神经元的特定末端区域，其中DA信号介导基于风险的决策是未知的。方法：采用微量输注D1/D2受体拮抗剂氟苯乙醇的方法，探讨大鼠眶额皮质（OFC）和伏隔核核壳区（AcbC和AcbS） D1/D2受体活性在风险选择中的调节作用。我们使用了一个风险贴现任务，即在特定的小奖励杠杆（总是提供1个球）和高风险的大奖励杠杆（提供4个球，但在随后的4个试验块中获得奖励的可能性越来越小）之间进行选择。为了验证任务对DA活性实验操作的敏感性，我们还研究了全身安非他明和氟苯乙醇的影响。结果：全身安非他明增加，全身氟苯硫醇减少风险选择。结果进一步表明，接受acbc内氟哌辛醇的大鼠能够追踪与风险杠杆相关的风险增加，但在所有试验区块中，包括初始试验区块（100%的大奖励），对风险杠杆的偏好普遍降低。向acb或OFC微量输注氟苯乙醇不会改变基于风险的决策。结论：我们的数据表明，acbc内D1/D2受体信号不支持追踪奖励概率变化的能力，但会影响基于风险的决策。也就是说，它增加了大鼠对已知与高风险相关成本相关的反应选项的偏好。
Background: It is well known that brain dopamine (DA) signals support risk-based decision making; however, the specific terminal regions of midbrain DA neurons through which DA signals mediate risk-based decision making are unknown.Methods: Using microinfusions of the D1/D2 receptor antagonist flupenthixol, we sought to explore the role of D1/D2 receptor activity in the rat orbitofrontal cortex (OFC) and core and shell regions of the nucleus accumbens (AcbC and AcbS, respectively) in the regulation of risky choices. A risk-discounting task was used that involves choices between a certain small-reward lever that always delivered 1 pellet or a risky large-reward lever which delivered 4 pellets but had a decreasing probability of receiving the reward across 4 subsequent within-session trial blocks (100%, 50%, 25%, 12.5%). To validate task sensitivity to experimental manipulations of DA activity, we also examined the effects of systemic amphetamine and flupenthixol.Results: Systemic amphetamine increased while systemic flupenthixol reduced risky choices. Results further demonstrate that rats that received intra-AcbC flupenthixol were able to track increasing risk associated with the risky lever but displayed a generally reduced preference for the risky lever across all trial blocks, including in the initial trial block (large reward at 100%). Microinfusions of flupenthixol into the AcbS or OFC did not alter risk-based decision making.Conclusions: Our data suggest that intra-AcbC D1/D2 receptor signaling does not support the ability to track shifts in reward probabilities but does bias risk-based decision making. That is, it increased the rats' preference for the response option known to be associated with higher risk-related costs.