Nicotine exposure leads to deficits in differential cued fear conditioning in mice and humans: A potential role of the anterior cingulate cortex

NEUROSCIENCE LETTERS

卷:673

Article

Kutlu, Munir Gunes¹  Marin, Marie-France²  Tumolo, Jessica M.³  Kaur, Navneet⁴  VanElzakker, Michael B.^4,5,6  Shin, Lisa M.^4,5,6  Gould, Thomas J.¹ 

[1] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA

[2] Univ Montreal, Montreal Mental Hlth Univ Inst, Dept Psychiat, Res Ctr, Montreal, PQ, Canada

[3] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA

[4] Tufts Univ, Dept Psychol, Medford, MA 02155 USA

[5] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[6] Harvard Med Sch, Dept Psychiat, Boston, MA USA

关键词: Nicotine;    Fear conditioning;    Skin conductance responses;    PTSD;    fMRI;   

DOI  :  10.1016/j.neulet.2018.03.002

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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