Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, SHM B404, New Haven, CT 06510, USA.
Psychopharmacology (Berl). 2012 Jan;219(2):363-75. doi: 10.1007/s00213-011-2520-0. Epub 2011 Oct 7.
Subjective values of actions are influenced by the uncertainty and immediacy of expected rewards. Multiple brain areas, including the prefrontal cortex and basal ganglia, are implicated in selecting actions according to their subjective values. Alterations in these neural circuits, therefore, might contribute to symptoms of impulsive choice behaviors in disorders such as substance abuse and attention-deficit hyperactivity disorder (ADHD). In particular, the α-2A noradrenergic system is known to have a key influence on prefrontal cortical circuits, and medications that stimulate this receptor are currently in use for the treatment of ADHD.
We tested whether the preference of rhesus monkeys for delayed and uncertain reward is influenced by the α-2A adrenergic receptor agonist, guanfacine.
In each trial, the animal chose between a small, certain and immediate reward and another larger, more delayed reward. In half of the trials, the larger reward was certain, whereas in the remaining trials, the larger reward was uncertain.
Guanfacine increased the tendency for the animal to choose the larger and more delayed reward only when it was certain. By applying an econometric model to the animal's choice behavior, we found that guanfacine selectively reduced the animal's time preference, increasing their choice of delayed, larger rewards, without significantly affecting their risk preference.
In combination with previous findings that guanfacine improves the efficiency of working memory and other prefrontal functions, these results suggest that impulsive choice behaviors may also be ameliorated by strengthening prefrontal functions.
行为的主观价值受到预期奖励的不确定性和即时性的影响。包括前额叶皮层和基底神经节在内的多个大脑区域，都参与根据主观价值选择行为。因此，这些神经回路的改变可能导致物质滥用和注意缺陷多动障碍（ADHD）等疾病中冲动选择行为的症状。特别是，α-2A 去甲肾上腺素能系统被认为对前额叶皮质回路有重要影响，目前用于治疗 ADHD 的药物刺激该受体。
我们测试了α-2A 肾上腺素能受体激动剂胍法辛是否会影响恒河猴对延迟和不确定奖励的偏好。
在每次试验中，动物在小的、确定的和即时的奖励与另一个更大的、更延迟的奖励之间进行选择。在一半的试验中，较大的奖励是确定的，而在其余的试验中，较大的奖励是不确定的。
胍法辛仅在较大的奖励确定时增加了动物选择较大和更延迟奖励的倾向。通过将计量经济学模型应用于动物的选择行为，我们发现胍法辛选择性地降低了动物的时间偏好，增加了它们对延迟、较大奖励的选择，而对风险偏好没有显著影响。
结合胍法辛改善工作记忆和其他前额叶功能效率的先前发现，这些结果表明，通过增强前额叶功能，也可能改善冲动选择行为。
