Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations
Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations
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DOI：
10.1037/0735-7044.113.5.891
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发表时间：
1999-10-01
影响因子：
1.9
通讯作者：
LeDoux, JE
中科院分区：
文献类型：
--
作者：
Nader, K;LeDoux, JE
以前的研究结果表明，系统性多巴胺能操纵损害巴甫洛夫条件性恐惧的检索。采用二级恐惧条件反射实验范式，研究腹侧被盖区（VTA）向杏仁核外侧区和基底区（LBA）的多巴胺能投射是否影响条件性恐惧。第一阶段需要条件刺激-非条件刺激（CSI-US）配对。在第2阶段，在CS2（第二个提示）与CS 1配对之前，在LBA或VTA中输注药物。在阶段3中，在没有药物的情况下测试由CS2引起的冻结行为。输注D2激动剂quinpirole到VTA或D1拮抗剂SCH 23390到LBA引起减少冻结到CS2。两种操作都降低了LBA中的DI受体活化。将D1激动剂SKF 38393输注到LBA中没有效果。这种结果模式与以下假设一致：腹侧被盖区-LBA多巴胺能投射调节CS和足电击US之间关联的恢复。
Previous findings have demonstrated that systemic dopaminergic manipulations impair the retrieval of Pavlovian conditioned fear. A second-order fear-conditioning paradigm was used to test whether the dopaminergic projection from the ventral tegmental area (VTA) to the lateral and basal amygdala (LBA) can affect conditioned fear. Phase I entailed conditioned stimulus-unconditioned stimulus (CSI-US) pairings. In Phase 2, drugs were infused in either the LBA or VTA prior to pairings of CS2 (a second cue) with CS1. In Phase 3, freezing behavior elicited by CS2 was tested without drugs. Infusions of the D2 agonist quinpirole into the VTA or of the D1 antagonist SCH 23390 into the LBA caused a decrease in freezing to CS2. Both manipulations decrease DI receptor activation in the LBA. Infusions of the D1 agonist SKF 38393 into the LBA had no effect. This pattern of results is consistent with the hypothesis that the VTA-LBA dopaminergic projection modulates the retrieval of an association between a CS and footshock US.