Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats
Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats
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DOI：
10.1523/jneurosci.22-06-02343.2002
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发表时间：
2002-03-15
影响因子：
5.3
通讯作者：
Davis, M
中科院分区：
文献类型：
--
作者：
Walker, DL;Ressler, KJ;Davis, M
NMDA受体拮抗剂阻断条件性恐惧消退时，全身注射，也直接注入杏仁核。在这里，我们评估的能力D-环丝氨酸（DCS），在士的宁不敏感的甘氨酸识别位点的NMDA受体复合物的部分激动剂，以促进条件性恐惧消退后，全身给药或内杏仁核infussions.Rats接受了10对3.7秒的光和0.4 mA的足电击（恐惧条件）。随后在没有电击的情况下呈现30、60或90次光之前和之后测量了恐惧增强的惊吓（有光与无光的惊吓增加）（消退训练）。30个非增强光呈现产生适度消光，60或90个呈现产生几乎完全消光（实验1）。DCS注射（3.25，15，或30毫克/公斤）前30个非增强光暴露剂量依赖性增强消光（实验2），但没有影响恐惧增强惊吓大鼠没有接受消光训练（实验3）。这些作用被HA-966阻断，HA-966是甘氨酸识别位点的拮抗剂（实验4）。DCS和HA-966在测试前注射时都没有改变恐惧增强的惊吓（实验5）。通过杏仁核内DCS（10微克/侧）输注来模拟全身给药的效果（实验6）。这些结果表明，全身或杏仁核内给药后促进NMDA受体活性的治疗可促进条件性恐惧的消除。
NMDA receptor antagonists block conditioned fear extinction when injected systemically and also when infused directly into the amygdala. Here we evaluate the ability of D-cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine-recognition site on the NMDA receptor complex, to facilitate conditioned fear extinction after systemic administration or intra-amygdala infusions.Rats received 10 pairings of a 3.7 sec light and a 0.4 mA footshock (fear conditioning). Fear-potentiated startle (increased startle in the presence vs the absence of the light) was subsequently measured before and after 30, 60, or 90 presentations of the light without shock (extinction training). Thirty non-reinforced light presentations produced modest extinction, and 60 or 90 presentations produced nearly complete extinction (experiment 1). DCS injections (3.25, 15, or 30 mg/kg) before 30 non-reinforced light exposures dose-dependently enhanced extinction (experiment 2) but did not influence fear-potentiated startle in rats that did not receive extinction training (experiment 3). These effects were blocked by HA-966, an antagonist at the glycine-recognition site (experiment 4). Neither DCS nor HA-966 altered fear-potentiated startle when injected before testing (experiment 5). The effect of systemic administration was mimicked by intra-amygdala DCS (10 mug/side) infusions (experiment 6).These results indicate that treatments that promote NMDA receptor activity after either systemic or intra-amygdala administration promote the extinction of conditioned fear.