Dopaminergic Modulation of Risk-Based Decision Making
Dopaminergic Modulation of Risk-Based Decision Making
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DOI：
10.1038/npp.2008.121
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发表时间：
2009-02-01
影响因子：
7.6
通讯作者：
Floresco, Stan B.
中科院分区：
文献类型：
--
作者：
St Onge, Jennifer R.;Floresco, Stan B.
精神药理学研究表明，中脑边缘多巴胺（DA）系统参与了对延迟或努力相关成本的成本/收益评估。然而，数据分析在基于风险的决策中的作用仍然相对未被探索。本研究利用概率贴现任务，考察了数据传递的系统性操纵对风险选择的影响。在离散试验中，大鼠在两种杠杆之间做出选择；按下“小/确定”的杠杆总是会得到一个奖励颗粒，而按下另一个“大/有风险”的杠杆则会得到四个奖励颗粒，但在四个试验块（100,50,25,12.5%）中，获得奖励的概率有所下降。在不同的训练有素的大鼠组中，我们评估了DA释放剂安非他明以及受体选择性激动剂和拮抗剂的作用。安非他明持续增加对大/高风险杠杆的偏好；同时使用D-1 （SCH23390）或D-2 （eticlopride）受体拮抗剂可阻断或减弱该效应。单独阻断这些受体中的任何一个都会引起风险规避。相反，刺激D-1 （SKF81297）或D-2（溴隐亭）受体也会增加风险选择。相比之下，PD128,907激活D-3受体减少了大/高风险杠杆的选择。同样，D-3与纳伐他胺的拮抗作用增强了安非他明诱导的风险选择的增加。阻断或刺激D-4受体不能可靠地改变行为。这些发现表明，DA在介导基于风险的决策中起着关键作用，D-1和D-2受体的激活增加使选择倾向于更大的概率奖励，而D-3受体似乎在这种决策形式中发挥相反的作用。
Psychopharmacological studies have implicated the mesolimbic dopamine (DA) system in the mediation of cost/benefit evaluations about delay or effort-related costs associated with larger rewards. However, the role of DA in risk-based decision making remains relatively unexplored. The present study investigated the effects of systemic manipulations of DA transmission on risky choice using a probabilistic discounting task. Over discrete trials, rats chose between two levers; a press on the 'small/certain' lever always delivered one reward pellet, whereas a press on the other, 'large/risky' lever delivered four pellets, but the probability of receiving reward decreased across the four trial blocks (100, 50, 25, 12.5%). In separate groups of well-trained rats we assessed the effects of the DA releaser amphetamine, as well as receptor selective agonists and antagonists. Amphetamine consistently increased preference for the large/risky lever; an effect that was blocked or attenuated by co-administration of either D-1 (SCH23390) or D-2 (eticlopride) receptor antagonists. Blockade of either of these receptors alone induced risk aversion. Conversely, stimulation of D-1 (SKF81297) or D-2 (bromocriptine) receptors also increased risky choice. In contrast, activation of D-3 receptors with PD128,907 reduced choice of the large/risky lever. Likewise, D-3 antagonism with nafadotride potentiated the amphetamine-induced increase in risky choice. Blockade or stimulation of D-4 receptors did not reliably alter behavior. These findings indicate that DA has a critical role in mediating risk-based decision making, with increased activation of D-1 and D-2 receptors biasing choice toward larger, probabilistic rewards, whereas D-3 receptors appear to exert opposing effects on this form of decision making.