Impaired cognitive flexibility in visual reversal-learning tasks has been observed in a wide range of neurological and neuropsychiatric disorders. Although both human and animal studies have implicated striatal D2-like and D1-like receptors (D2R; D1R) in this form of flexibility, less is known about the contribution they make within distinct sub-regions of the striatum and the different phases of visual reversal learning. The present study investigated the involvement of D2R and D1R during the early (perseverative) phase of reversal learning as well as in the intermediate and late stages (new learning) after microinfusions of D2R and D1R antagonists into the nucleus accumbens core and shell (NAcC; NAcS), the anterior and posterior dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) on a touchscreen visual serial reversal-learning task. Reversal learning was improved after dopamine receptor blockade in the nucleus accumbens; the D1R antagonist, SCH23390, in the NAcS and the D2R antagonist, raclopride, in the NAcC selectively reduced early, perseverative errors. In contrast, reversal learning was impaired by D2R antagonism, but not D1R antagonism, in the dorsal striatum: raclopride increased errors in the intermediate phase after DMS infusions, and increased errors across phases after DLS infusions. These findings indicate that D1R and D2R modulate different stages of reversal learning through effects localised to different sub-regions of the striatum. Thus, deficits in behavioral flexibility observed in disorders linked to dopamine perturbations may be attributable to specific D1R and D2R dysfunction in distinct striatal sub-regions.

中文翻译：

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背侧和腹侧纹状体多巴胺 D1 和 D2 受体差异调节连续视觉逆转学习的不同阶段。


在多种神经系统和神经精神疾病中都观察到视觉逆转学习任务中认知灵活性受损。尽管人类和动物研究都表明纹状体 D2 样受体和 D1 样受体（D2R；D1R）具有这种形式的灵活性，但人们对它们在纹状体不同亚区域和视觉不同阶段的贡献知之甚少。逆向学习。本研究调查了 D2R 和 D1R 在逆转学习的早期（持续）阶段以及将 D2R 和 D1R 拮抗剂微量输注到伏核核和壳（NAcC；NAcC； NAcS）、前、后背内侧纹状体（DMS）和背外侧纹状体（DLS）在触摸屏视觉串行逆向学习任务中的表现。伏隔核多巴胺受体阻断后，逆转学习能力得到改善； NAcS 中的 D1R 拮抗剂 SCH23390 和 NAcC 中的 D2R 拮抗剂雷氯必利选择性减少早期、持续性错误。相比之下，背侧纹状体中的逆转学习受到 D2R 拮抗作用的损害，但不受 D1R 拮抗作用的影响：雷氯必利增加了 DMS 输注后中间阶段的错误，并且增加了 DLS 输注后跨阶段的错误。这些发现表明，D1R 和 D2R 通过纹状体不同子区域的效应来调节逆转学习的不同阶段。因此，在与多巴胺扰动相关的疾病中观察到的行为灵活性缺陷可能归因于不同纹状体亚区域中特定的 D1R 和 D2R 功能障碍。