Pulsed nicotine infusions as a model for smoking: validating a tool to explore nicotine thresholds in humans.

IF 3.5 3区医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-09-01 Epub Date: 2024-07-06 DOI:10.1007/s00213-024-06609-6

Suprit Parida, R Ross MacLean, Ralitza Gueorguieva, Mehmet Sofuoglu

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Abstract

Rationale: No previous studies examined the discriminative stimulus effects of intravenous (IV) nicotine in humans.

Objectives: To evaluate a pulsed IV nicotine infusion procedure designed to mimic inhaled nicotine delivery and to identify a range of nicotine doses that may capture the threshold doses for the subjective and discriminative stimulus effects of nicotine. By determining these thresholds, we can gain valuable insights into the addictive threshold of nicotine.

Methods: Eleven participants had 2 Test Sessions following overnight abstinence from smoking. Test Session 1 examined participants' ability to discriminate 0.1 mg nicotine/pulse nicotine from saline. Test Session 2 examined if participants can discriminate 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine from saline. These nicotine doses were delivered as a cluster of 4 pulsed-nicotine infusions of 2-second duration with a 28-second interval between each pulse.

Results: The lowest doses of nicotine that produced greater responses than saline for discrimination, subjective effects, and heart rate ranged from 0.05 to 0.1 mg nicotine/pulse.

Conclusions: These findings support the validity of our pulsed-infusion procedure as a model for nicotine delivery by smoking and its utility in examining factors that may impact the addictive threshold of nicotine.

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将脉冲尼古丁输注作为吸烟模型：验证探索人体尼古丁阈值的工具。

理由：以前没有研究考察过静脉注射尼古丁对人体的辨别刺激作用：评估旨在模拟吸入尼古丁给药的脉冲式静脉注射尼古丁程序，并确定尼古丁剂量范围，以捕捉尼古丁主观和辨别刺激效应的阈值剂量。通过确定这些阈值，我们可以深入了解尼古丁的成瘾阈值：11 名参与者在一夜戒烟后进行了 2 次测试。测试环节 1 考察参与者从生理盐水中分辨出 0.1 毫克尼古丁/脉冲尼古丁的能力。测试环节 2 检验参与者从生理盐水中辨别 0.05、0.025 和 0.0125 毫克尼古丁/脉冲尼古丁的能力。这些尼古丁剂量是以 4 个持续时间为 2 秒的脉冲尼古丁输注群的形式提供的，每个脉冲之间的间隔为 28 秒：结果：尼古丁的最低剂量在辨别力、主观效应和心率方面产生的反应大于生理盐水，其范围为 0.05 至 0.1 毫克尼古丁/脉冲：这些研究结果证明了我们的脉冲灌注程序作为尼古丁吸食递送模型的有效性，以及它在研究可能影响尼古丁成瘾阈值的因素方面的实用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.