Nicotine exposure leads to deficits in differential cued fear conditioning in mice and humans: A potential role of the anterior cingulate cortex.
Nicotine exposure leads to deficits in differential cued fear conditioning in mice and humans: A potential role of the anterior cingulate cortex.
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DOI：
10.1016/j.neulet.2018.03.002
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发表时间：
2018-04-23
影响因子：
2.5
通讯作者：
Gould TJ
中科院分区：
文献类型：
--
作者：
Kutlu MG;Marin MF;Tumolo JM;Kaur N;VanElzakker MB;Shin LM;Gould TJ
创伤后应激障碍(PTSD)等应激和焦虑症的特点是安全学习中断。吸烟与压力和焦虑症症状密切相关，既是一个促成因素，也是一个易受伤害的因素。我们实验室的啮齿动物研究最近表明，急性和慢性尼古丁暴露会扰乱安全学习。然而，目前尚不清楚尼古丁的这些影响是否会转移到人类身上。目前的研究通过对小鼠和人类实施翻译差异线索恐惧条件反射范式来解决这一差距。在小鼠身上，我们发现，在获取和测试过程中，长期接触尼古丁降低了发出危险信号的条件刺激(CS+)和发出安全信号的条件刺激(CS−)之间的区别。然后，我们在接受功能磁共振成像(FMRI)的吸烟者和非吸烟者中使用了类似的差异线索恐惧条件反射范式。与非吸烟者相比，吸烟者在恐惧条件反射过程中对CS+/CS−的辨别能力降低。此外，使用功能磁共振成像，我们发现在不同线索的恐惧条件反射中，吸烟者的亚膝部和背侧扣带回皮质的激活低于非吸烟者。这些结果表明了一种潜在的生物学机制，这种机制潜藏在一种不受调控的区分危险和安全线索的能力之下。我们的结果表明，尼古丁暴露对小鼠和人类安全学习的影响之间存在明显的相似之处，因此表明吸烟可能是无法处理与危险和安全相关线索相关信息的风险因素。
Stress and anxiety disorders such as posttraumatic stress disorder (PTSD) are characterized by disrupted safety learning. Tobacco smoking has been strongly implicated in stress and anxiety disorder symptomatology, both as a contributing factor and as a vulnerability factor. Rodent studies from our lab have recently shown that acute and chronic nicotine exposure disrupts safety learning. However, it is unknown if these effects of nicotine translate to humans. The present studies addressed this gap by administering a translational differential cued fear conditioning paradigm to both mice and humans. In mice, we found that chronic nicotine exposure reduced discrimination between a conditioned stimulus (CS) that signals for danger (CS+) and another CS that signals for safety (CS−) during both acquisition and testing. We then employed a similar differential cued fear conditioning paradigm in human smokers and non-smokers undergoing functional magnetic resonance imaging (fMRI). Smokers showed reduced CS+/CS− discrimination during fear conditioning compared to non-smokers. Furthermore, using fMRI, we found that subgenual and dorsal anterior cingulate cortex activations were lower in smokers than in non-smokers during differential cued fear conditioning. These results suggest a potential biological mechanism underlying a dysregulated ability to discriminate between danger and safety cues. Our results indicate a clear parallel between the effects of nicotine exposure on safety learning in mice and humans and therefore suggest that smoking might represent a risk factor for inability to process information related to danger and safety related cues.
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影响因子：
4.7
作者：
Jovanovic T;Kazama A;Bachevalier J;Davis M
通讯作者：
Davis M
影响因子：
4.3
作者：
Hughes KC;Shin LM
通讯作者：
Shin LM
影响因子：
2.7
作者：
Gould, TJ;Higgins, JS
通讯作者：
Higgins, JS
影响因子：
--
作者：
Koenen, KC;Hitsman, B;Tsuang, M
通讯作者：
Tsuang, M
DOI：
10.1007/bf02688830
发表时间：
2003-04-01
期刊：
INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE
影响因子：
--
作者：
Gould, TJ
通讯作者：
Gould, TJ