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多巴胺D2受体在条件性恐惧表达中的机制。

Dopamine D2 receptor mechanisms in the expression of conditioned fear.

作者信息

de Oliveira Amanda Ribeiro, Reimer Adriano Edgar, Brandão Marcus Lira

机构信息

Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil.

出版信息

Pharmacol Biochem Behav. 2006 May;84(1):102-11. doi: 10.1016/j.pbb.2006.04.012. Epub 2006 Jun 15.

Abstract

The increase in the startle reflex in the presence of a stimulus that has been previously paired to foot shock is taken as an index of anxiety and named fear potentiated startle (FPS). Freezing behavior, defined as a cessation of all observable movements except those associated with respiration, has also been used as an index of fear in rats. Recently, a growing body of evidence has suggested that dopaminergic mechanisms are significant for different aspects of affective memory, namely its formation, expression or retrieval. However, the results of studies that have directly examined the ability of the dopaminergic system to influence fear have been inconsistent. This work is aimed at examining the involvement of D1 and D2 receptors in the acquisition and expression of conditioned fear using the fear potentiated startle test and the freezing behavior. We evaluated the effects of systemic administration of the D1 antagonist SCH 23390, the D1 agonist SKF 38393, the D2 antagonist sulpiride and the D2 agonist quinpirole before and after conditioning on FPS and freezing as indices of fear memory. The motor activity of the animals was also evaluated in an open field test. Injections of SCH 23390, SKF 38393, sulpiride and quinpirole before conditioning sessions did not produce any significant effect on FPS, but SCH 23390 decreased freezing. Injections of SCH 23390, SKF 38393 and sulpiride before testing session did not produce any significant effect on FPS or freezing. Quinpirole caused significant reduction in FPS and freezing when injected before testing. Drugs' actions were not due to nonspecific impairments in the ability to respond to the CS because the identical drug treatments had no effect in an open field test. Our findings indicate that DA mechanisms mediated by D2 receptors are mainly involved in the expression rather than in the acquisition of fear.

摘要

在先前与足部电击配对的刺激出现时,惊吓反射增强被视为焦虑指标,并被称为恐惧增强惊吓(FPS)。静止行为被定义为除与呼吸相关的动作外所有可观察到的动作停止,它也被用作大鼠恐惧的指标。最近,越来越多的证据表明多巴胺能机制在情感记忆的不同方面,即其形成、表达或提取中具有重要意义。然而,直接研究多巴胺能系统影响恐惧能力的研究结果并不一致。这项工作旨在使用恐惧增强惊吓测试和静止行为来研究D1和D2受体在条件性恐惧的获得和表达中的作用。我们评估了在条件反射前后全身给予D1拮抗剂SCH 23390、D1激动剂SKF 38393、D2拮抗剂舒必利和D2激动剂喹吡罗对作为恐惧记忆指标的FPS和静止行为的影响。还在旷场试验中评估了动物的运动活性。在条件反射训练前注射SCH 23390、SKF 38393、舒必利和喹吡罗对FPS没有产生任何显著影响,但SCH 23390降低了静止行为。在测试前注射SCH 23390、SKF 38393和舒必利对FPS或静止行为没有产生任何显著影响。喹吡罗在测试前注射时导致FPS和静止行为显著降低。药物的作用不是由于对条件刺激反应能力的非特异性损害,因为相同的药物治疗在旷场试验中没有效果。我们的研究结果表明,由D2受体介导的多巴胺能机制主要参与恐惧的表达而非获得。

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