Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior
Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior
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DOI：
10.1007/s00213-008-1341-2
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发表时间：
2009-03-01
影响因子：
3.4
通讯作者：
Robbins, Trevor W.
中科院分区：
文献类型：
--
作者：
Boulougouris, Vasileios;Castane, Anna;Robbins, Trevor W.
多巴胺与改变行为的能力密切相关，以应对不断变化的刺激-奖励偶然性。我们研究了全身给予D2/D3受体激动剂喹吡罗的影响（0.1，0.3 mg/kg），D2/D3受体拮抗剂雷氯必利（0.1，0.3 mg/kg），选择性D3拮抗剂萘法多曲胺（0.3、1.0 mg/kg），和雷氯必利联合给药（0.1 mg/kg）或萘法多曲胺（1.0 mg/kg）与喹吡罗（0.3 mg/kg）合用对大鼠空间辨别和反转学习的影响。两个杠杆都被提出来了，只有一个得到了加强。要求大鼠在固定比率3的强化时间表下对强化杠杆作出反应。在达到标准后，引入逆转。在保留先前加强的应急期间，没有药物改变性能。Quinpirole（0.3毫克/公斤）显着受损的逆转学习，通过增加试验和不正确的反应，标准在逆转阶段，表现为增加持续反应的行为模式，在以前加强杠杆。相比之下，无论是雷氯必利或萘法多曲胺单独给药时，都不会改变逆转性能。然而，雷氯必利阻断了喹吡罗诱导的逆转缺陷，而萘法多曲胺和喹吡罗的联合给药不仅影响逆转期间的表现，而且还影响保留期。共同管理的萘多曲胺和quinpirole造成的逆转损害与持续和learning errors.Our的数据表明D2和D3受体在面对环境变化灵活地修改行为的能力中的不同作用。
Dopamine is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies.We investigated the effects of systemic administration of the D2/D3 receptor agonist quinpirole (0.1, 0.3 mg/kg), the D2/D3 receptor antagonist raclopride (0.1, 0.3 mg/kg), the selective D3 antagonist nafadotride (0.3, 1.0 mg/kg), and combined administration of raclopride (0.1 mg/kg) or nafadotride (1.0 mg/kg) with quinpirole (0.3 mg/kg) on spatial discrimination and reversal learning.Rats were trained on an instrumental two-lever spatial discrimination and reversal learning task. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a reversal was introduced.None of the drugs altered performance during retention of the previously reinforced contingencies. Quinpirole (0.3 mg/kg) significantly impaired reversal learning by increasing both trials and incorrect responses to criterion in reversal phase, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, neither raclopride nor nafadotride when administered alone altered reversal performance. However, raclopride blocked the quinpirole-induced reversal deficit, whereas combined administration of nafadotride and quinpirole affected not only performance during the reversal but also the retention phase. The reversal impairment resulting from co-administration of nafadotride and quinpirole was associated with both perseverative and learning errors.Our data indicate distinct roles for D2 and D3 receptors in the capacity to modify behavior flexibly in the face of environmental change.