University Medical Center Hamburg-Eppendorf (Germany), Department of Systems Neuroscience, Hamburg, Germany.
University Medical Center Hamburg-Eppendorf (Germany), Department of Child- and Adolescent Psychiatry and Psychotherapy, Hamburg, Germany.
Transl Psychiatry. 2024 Aug 3;14(1):319. doi: 10.1038/s41398-024-03040-5.
Nicotine intake is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in rodents and humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n = 88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to enhanced physiological arousal to learned threats and overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates of adaptive aversive learning in line with the risk for the development of pathological anxiety.
尼古丁摄入与焦虑障碍的维持和发展有关，并损害了啮齿动物和人类对威胁和安全的适应性辨别。然而，目前尚不清楚尼古丁是否对恐惧学习的情感和神经机制产生因果药理作用。我们进行了一项预先注册的、伪随机的、双盲的药物 fMRI 研究，以调查急性尼古丁对非吸烟者的恐惧获得和消退的影响（n=88）。我们的结果表明，尼古丁给药导致主观恐惧中对威胁和安全的辨别力下降。与安慰剂对照组相比，尼古丁还降低了海马体中（威胁与安全相比）的差异激活，而海马体与伏隔核和杏仁核在功能上是耦合的。此外，尼古丁导致对学习威胁的生理唤醒增强，并过度激活腹侧被盖区。这项研究提供了机制证据，表明单次尼古丁剂量会损害适应性厌恶学习的神经基质，从而增加病理性焦虑的发展风险。
