The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice
The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice
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DOI：
10.1101/lm.88805
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发表时间：
2005-05-01
影响因子：
2
通讯作者：
Barad, M
中科院分区：
文献类型：
--
作者：
Cain, CK;Godsil, BP;Barad, M
我们最近报道，抑制学习的一种形式的恐惧消退，可以被系统地给予L类电压门控钙通道拮抗剂(包括硝苯地平)选择性地阻断。我们在这里重复这一发现，并检查在服用药物或硝苯地平(40 mg/kg)后，三种减少的偶发效应。在第一个实验中，通过将USS添加到训练协议(降级应急)中来实现应急减少，这被认为是一种与行为抑制无关的现象。在第二个实验中，通过改变CS-US配对的百分比来减少偶然性，这一现象被认为是弱依赖于行为抑制的。在第三和第四个实验中，通过在训练方案中添加CS(部分强化)来减少偶然性，这一现象被认为完全依赖于行为抑制。我们发现，硝苯地平没有削弱这些减少的偶发效应。在最后的实验中，我们发现消亡发生在获得后1或3小时，但不是立即进行，是依赖于LVGCC的。综上所述，这些结果表明，偶然性效应和消亡的减少依赖于不同的分子机制，而行为抑制的LVGCC依赖在联合CS-US学习后随着时间的推移而发展。
We recently reported that fear extinction, a form of inhibitory learning, is selectively blocked by systemic administration of L-type voltage-gated calcium channel (LVGCC) antagonists, including nifedipine, in mice. We here replicate this finding and examine three reduced contingency effects after vehicle or nifedipine (40 mg/kg) administration. In the first experiment, contingency reduction was achieved by adding USs to the training protocol (degraded contingency), a phenomenon thought to be independent of behavioral inhibition. In the second experiment, contingency reduction was achieved by varying the percentage of CS-US pairing, a phenomenon thought to be weakly dependent on behavioral inhibition. In the third and fourth experiments, contingency reduction was achieved by adding CSs to the training protocol (partial reinforcement), a phenomenon thought to be completely dependent on behavioral inhibition. We found that none of these reduced contingency effects was impaired by nifedipine. In a final experiment, we found that extinction conducted I or 3 h post-acquisition, but not immediately, was LVGCC-dependent. Taken together, the results suggest that reduced contingency effects and extinction depend on different molecular mechanisms and that LVGCC dependence of behavioral inhibition develops with time after associative CS-US learning.