Mueller Madeleine, Korn Christoph, Haaker Jan
Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistr.52, 20251, Hamburg, Germany.
Department of General Psychology and Cognitive Neuroscience, Charlotte Fresenius University, Alte Rabenstraße 32, 20148, Hamburg, Germany.
Psychopharmacology (Berl). 2025 Apr 22. doi: 10.1007/s00213-025-06789-9.
Developing adaptive strategies for survival relies on distinguishing danger from safety through aversive learning mechanisms. Chronic and acute nicotine exposure have been linked to impaired aversive learning and reduced discrimination between threat and safety. Yet, it is unclear if nicotine also impacts one behavioural consequence of aversive learning, which is the avoidance of threats.
This preregistered study examines how acute nicotine influences costly avoidance behaviour in non-smokers.
To this end, healthy non-smoking participants (n = 66) received either 1 mg nicotine or a placebo in a double-blind design and underwent an active avoidance task. During acquisition, participants could choose between a safer but longer path to reach their goal or a shorter path (less effort) with a higher chance of receiving an aversive outcome in the form of an electrical stimulus. During uninstructed extinction, both paths no longer contained the risk of an aversive outcome and participants could learn this new safety association by trial and error. Finally, an instructed extinction phase indicated complete safety.
Contrary to our pre-registered hypotheses, participants with nicotine intake showed a trendwise reduced avoidance of aversive outcomes, compared to placebo controls. Further analysis revealed however that nicotine did not enhance safety learning during extinction in the nicotine group, as compared to controls.
In conclusion, this study strengthens the evidence that nicotine alters learning to identify threat and safety, which is also transferred to avoidance behaviour.
通过厌恶学习机制区分危险与安全是制定适应性生存策略的基础。长期和短期接触尼古丁与厌恶学习受损以及威胁与安全辨别能力下降有关。然而，尼古丁是否也会影响厌恶学习的一种行为后果，即对威胁的回避，尚不清楚。
这项预先注册的研究探讨了急性尼古丁如何影响非吸烟者代价高昂的回避行为。
为此，健康的非吸烟参与者（n = 66）采用双盲设计，接受1毫克尼古丁或安慰剂，并进行主动回避任务。在习得阶段，参与者可以在一条更安全但更长的路径以达到目标，或者一条更短（省力）但遭受电刺激形式的厌恶结果几率更高的路径之间进行选择。在无指导的消退阶段，两条路径都不再有厌恶结果的风险，参与者可以通过试错来了解这种新的安全关联。最后，一个有指导的消退阶段表明完全安全。
与我们预先注册的假设相反，与安慰剂对照组相比，摄入尼古丁的参与者对厌恶结果的回避呈趋势性降低。然而，进一步分析表明，与对照组相比，尼古丁组在消退过程中并未增强安全学习。
总之，本研究进一步证明尼古丁会改变识别威胁和安全的学习，这种改变也会转移到回避行为上。
