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伏隔核和海马 D2 受体在焦虑和记忆中的调节作用。

The modulatory role of accumbens and hippocampus D2 receptors in anxiety and memory.

机构信息

Department of Biology, Faculty of Sciences, University of Zanjan, P.O.Box 45371-38791, Zanjan, Iran.

Cognitive and Neuroscience Research Center (CNRC), Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2018 Oct;391(10):1107-1118. doi: 10.1007/s00210-018-1534-0. Epub 2018 Jul 13.

Abstract

The present study investigated the role of dopamine D2 receptors (D2Rs) of the dorsal hippocampus (DH) and the nucleus accumbens (NAc) and the effect of their dopaminergic activities on anxiety-like behavior and aversive learning using a test-retest elevated plus-maze (EPM) paradigm in male Wistar rats. Guide cannulae were implanted to allow microinjection of D2R agonist quinpirole or antagonist sulpiride. The pre-test intra-NAc microinjection of quinpirole (0.0625-0.25 μg/rat) or sulpiride (0.125-0.5 μg/rat) increased the percentage of time spent in the open arms (%OAT) of EPM, suggesting an anxiolytic-like effect. However, an increase in open-arm avoidance was observed in the control rats when retested in the EPM, suggesting aversive information storage. Furthermore, a similar result was obtained in the quinpirole-treated rats. In contrast, the sulpiride-treated rats failed to demonstrate further open-arm avoidance, thus proposing an aversive learning deficit. The intra-DH microinjection of drugs alone induced an anxiolytic-like effect and learning deficit. The quinpirole (0.125 μg/rat) injected into each site had no effect on the response induced by sulpiride injected into another site. Finally, a subthreshold dose of quinpirole in both sites did not alter the %OAT; on the contrary, it preserved the aversive memory. The sulpiride induced an anxiolytic-like effect and a learning deficit. Our data suggests that the involvement of D2Rs in the interactions of DH-NAc dopaminergic system helps regulate anxiety-related behavior and EPM-associative memory.

摘要

本研究采用测试-重测高架十字迷宫(EPM)范式,探讨了背侧海马(DH)和伏隔核(NAc)中的多巴胺 D2 受体(D2Rs)的作用,以及它们的多巴胺能活动对雄性 Wistar 大鼠焦虑样行为和厌恶学习的影响。通过引导套管植入,可以进行 D2R 激动剂喹吡罗或拮抗剂舒必利的微注射。NAc 内预测试微注射喹吡罗(0.0625-0.25μg/大鼠)或舒必利(0.125-0.5μg/大鼠)增加了 EPM 中开放臂时间的百分比(%OAT),表明具有抗焦虑样作用。然而,当在 EPM 中重新测试时,对照组大鼠出现了开放臂回避增加,表明存储了厌恶信息。此外,在喹吡罗处理的大鼠中也获得了类似的结果。相比之下,舒必利处理的大鼠未能进一步表现出回避开放臂,因此提出了厌恶学习缺陷。单独给予药物对 DH 内微注射诱导出抗焦虑样作用和学习缺陷。注射到每个部位的 0.125μg 喹吡罗对注射到另一个部位的舒必利引起的反应没有影响。最后,两个部位的阈下剂量的喹吡罗没有改变 %OAT;相反,它保留了厌恶记忆。舒必利诱导了抗焦虑样作用和学习缺陷。我们的数据表明,DH-NAc 多巴胺能系统中 D2Rs 的参与有助于调节与焦虑相关的行为和 EPM 联想记忆。

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