Institute of Neuroscience, The Medical School, Newcastle University, Newcastle, NE2 4HH, UK.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Neuropharmacology. 2020 Jun 15;170:108063. doi: 10.1016/j.neuropharm.2020.108063. Epub 2020 Mar 24.
Across species, nicotine can produce robust discriminative stimulus (DS) effects, as with other drugs of abuse, a feature that has been harnessed to advance our understanding on the neuropharmacological mechanisms of nicotine's actions. With the crucial role played by nicotine in supporting tobacco dependence, nicotine DS effects have presented an ideal platform to develop novel generation of smoking cessation compounds. Findings from preclinical strands of research have invigorated the field of human discrimination research to objectively assess nicotine's interoceptive stimulus effects. As such, translation studies provide proof of concept for nicotine DS research as a method to assess the subjective effects of nicotine per se, separate from non-nicotine stimuli involved in smoking. Recent clinical studies with low doses have demonstrated that perceiving nicotine's DS effects is necessary, yet not sufficient, for that dose to be reinforcing. These measures have been instrumental in developing novel strategies with regards to establishing threshold doses of nicotine contained in tobacco products, to then determine subthreshold doses that cannot be discriminated and, therefore, fail to maintain reinforcement. Findings from preclinical and clinical nicotine DS research could substantially inform public health policies aimed at regulating nicotine content of consumer products so that they minimize risks of dependency. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.
在不同物种中，尼古丁可以产生强烈的辨别性刺激（DS）效应，就像其他成瘾药物一样，这一特征被用来深入了解尼古丁作用的神经药理学机制。由于尼古丁在支持烟草依赖方面的关键作用，尼古丁 DS 效应为开发新一代戒烟化合物提供了理想的平台。临床前研究的发现为人类辨别研究领域注入了活力，以客观评估尼古丁的内感受性刺激效应。因此，翻译研究为尼古丁 DS 研究提供了概念验证，作为一种评估尼古丁本身主观效应的方法，与吸烟中涉及的非尼古丁刺激因素分开。最近的低剂量临床研究表明，感知尼古丁的 DS 效应是必要的，但不足以使该剂量具有强化作用。这些措施对于制定烟草制品中尼古丁含量的阈值剂量，然后确定无法辨别且因此无法维持强化作用的亚阈值剂量具有重要意义。临床前和临床尼古丁 DS 研究的结果可以为旨在监管消费产品中尼古丁含量的公共卫生政策提供重要信息，以最大程度地降低依赖风险。本文是“当代尼古丁神经药理学进展”特刊的一部分。
