Raybuck Jonathan D, Gould Thomas J
Department of Psychology, Temple University, Philadelphia, PA 19122, USA.
Behav Neurosci. 2007 Oct;121(5):1119-24. doi: 10.1037/0735-7044.121.5.1119.
Contextual fear conditioning is enhanced by nicotine, but the cellular mechanisms underlying this effect are unknown. Extracellular signal regulated kinase 1/2 (ERK 1/2) has been shown to play an integral role in the formation of contextual fear memories. As such, it is possible that ERK 1/2 is involved in the enhancement of contextual fear conditioning by nicotine. To determine whether ERK 1/2 plays a role in this enhancement, a dose of SL327 (a selective, systemic ERK 1/2 inhibitor) that is subthreshold for inhibiting contextual fear conditioning was coadministered with nicotine prior to training, testing, or both training and testing of contextual fear conditioning in C57BL/6 mice. When administered prior to training, this subthreshold dose of SL327 attenuated the enhancement of contextual fear conditioning by nicotine to levels similar to those of vehicle-treated animals. When administered prior to testing, the subthreshold dose of SL327 did not significantly alter conditioning. These results suggest that activation of ERK 1/2 by nicotine during acquisition leads to an enhancement of contextual fear conditioning.
情境恐惧条件反射会因尼古丁而增强，但其背后的细胞机制尚不清楚。细胞外信号调节激酶1/2（ERK 1/2）已被证明在情境恐惧记忆的形成中起重要作用。因此，ERK 1/2有可能参与尼古丁对情境恐惧条件反射的增强作用。为了确定ERK 1/2是否在这种增强作用中发挥作用，在C57BL/6小鼠进行情境恐惧条件反射训练、测试或训练与测试之前，将低于抑制情境恐惧条件反射阈值剂量的SL327（一种选择性的全身性ERK 1/2抑制剂）与尼古丁共同给药。当在训练前给药时，这种低于阈值剂量的SL327将尼古丁对情境恐惧条件反射的增强作用减弱到与给予赋形剂处理动物相似的水平。当在测试前给药时，低于阈值剂量的SL327没有显著改变条件反射。这些结果表明，在习得过程中尼古丁激活ERK 1/2会导致情境恐惧条件反射增强。
