Effects of α-2A adrenergic receptor agonist on time and risk preference in primates
Effects of α-2A adrenergic receptor agonist on time and risk preference in primates
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DOI：
10.1007/s00213-011-2520-0
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发表时间：
2012-01-01
影响因子：
3.4
通讯作者：
Lee, Daeyeol
中科院分区：
文献类型：
--
作者：
Kim, Soyoun;Bobeica, Irina;Lee, Daeyeol
行动的主观价值受到预期回报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了根据主观价值选择行动。因此，这些神经回路的改变可能会导致物质滥用和注意力缺陷多动障碍（ADHD）等疾病的冲动选择行为症状。特别是，已知α-2A去甲肾上腺素能系统对前额叶皮层回路具有关键影响，并且刺激该受体的药物目前用于治疗ADHD。我们测试了恒河猴对延迟和不确定奖励的偏好是否受到α-2A肾上腺素能受体激动剂胍法辛的影响。在每次试验中，动物在小的，一个是更大的，更大的奖励。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，胍法辛增加了动物选择较大和更延迟奖励的倾向，只有当它是确定的。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，增加了它们对延迟的、更大的奖励的选择，而没有显著影响它们的风险偏好。结合之前关于胍法辛提高工作记忆和其他前额叶功能效率的研究结果，这些结果表明，冲动选择行为也可能通过加强前额叶功能而得到改善。
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 alpha-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 alpha-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.