Mai Bettina, Sommer Susanne, Hauber Wolfgang
Department Animal Physiology, University of Stuttgart, Stuttgart, Germany (Mrs Mai, Sommer, and Dr Hauber).
Int J Neuropsychopharmacol. 2015 Apr 23;18(10):pyv043. doi: 10.1093/ijnp/pyv043.
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.
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.
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.
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.
众所周知，脑多巴胺（DA）信号支持基于风险的决策；然而，中脑DA神经元通过其信号介导基于风险的决策的具体终末区域尚不清楚。
我们使用D1/D2受体拮抗剂氟哌噻吨进行微量注射，旨在探究D1/D2受体活性在大鼠眶额皮质（OFC）以及伏隔核核心区和壳区（分别为AcbC和AcbS）对风险选择调节中的作用。采用了一种风险折扣任务，该任务涉及在一个总是提供1颗食丸的确定性小奖励杠杆和一个提供4颗食丸但在随后4个会话内试验块中获得奖励的概率逐渐降低（100%、50%、25%、12.5%）的风险大奖励杠杆之间进行选择。为了验证该任务对DA活性实验操作的敏感性，我们还研究了全身性苯丙胺和氟哌噻吨的作用。
全身性苯丙胺增加了风险选择，而全身性氟哌噻吨降低了风险选择。结果进一步表明，接受AcbC内氟哌噻吨注射的大鼠能够追踪与风险杠杆相关的风险增加，但在所有试验块中，包括初始试验块（100%获得大奖励），对风险杠杆的总体偏好降低。向AcbS或OFC微量注射氟哌噻吨不会改变基于风险的决策。
我们的数据表明，AcbC内D1/D2受体信号传导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更高风险相关成本相关的反应选项的偏好。
