Behavioral flexibility, which allows organisms to adapt their actions in response to environmental changes, is impaired in a number of neuropsychiatric conditions, including obsessive-compulsive disorder and addiction. Studies in human subjects and monkeys have reported correlations between individual differences in dopamine D2-type receptor (D2R) levels in the caudate nucleus and performance in a discrimination reversal task, in which established contingent relationships between abstract stimuli and rewards (or punishments) are reversed. Global genetic deletion of the D2R in mice disrupts reversal performance, indicating a likely causal role for this receptor in supporting flexible behaviors. To directly examine the specific role of caudate D2-type receptors in reversal performance, the D2/3/4R agonist quinpirole was infused via chronic indwelling cannulae into the medial caudate of male and female marmoset monkeys performing a touchscreen-based serial discrimination reversal task. Given prior evidence for dose-dependent effects of quinpirole and other dopaminergic drugs, a full dose-response curve was established. Individually, marmosets displayed marked differences in behavioral sensitivity to specific doses of intra-caudate quinpirole. Collectively, they exhibited a behaviorally specific bi-phasic deficit in reversal learning, being consistently impaired at both relatively low and high doses of quinpirole. However, intermediate doses of intra-caudate quinpirole produced significant improvement in reversal performance. These data support previous human and monkey neuroimaging studies by providing causal evidence of a U-shaped function describing how dopamine modulates cognitive flexibility in the primate striatum.

中文翻译：

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狨猴的 D2 受体和认知灵活性：纹状体内喹吡罗对连续逆转性能的三相剂量反应效应。

允许生物体根据环境变化调整其行为的行为灵活性在许多神经精神疾病中受损，包括强迫症和成瘾。对人类受试者和猴子的研究报告了尾状核中多巴胺 D2 型受体 (D2R) 水平的个体差异与辨别逆转任务的表现之间的相关性，其中抽象刺激与奖励（或惩罚）之间已建立的或有关系被逆转. 小鼠中 D2R 的全局基因缺失破坏了逆转性能，表明该受体在支持灵活行为方面可能具有因果作用。为了直接检查尾状 D2 型受体在逆转性能中的特定作用，D2/3/4R 激动剂喹吡罗通过长期留置套管注入雄性和雌性狨猴的内侧尾状核，执行基于触摸屏的串行辨别逆转任务。鉴于先前关于喹吡罗和其他多巴胺能药物的剂量依赖性作用的证据，建立了完整的剂量反应曲线。个别地，狨猴对特定剂量的尾状喹吡罗的行为敏感性表现出显着差异。总的来说，他们在逆向学习中表现出行为特异性的双相缺陷，在相对低剂量和高剂量的喹吡罗下持续受损。然而，中等剂量的尾状内喹吡罗在逆转性能方面产生了显着改善。