Animal models to assess the abuse liability of tobacco products: Effects of smokeless tobacco extracts on intracranial self-stimulation
Animal models to assess the abuse liability of tobacco products: Effects of smokeless tobacco extracts on intracranial self-stimulation
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DOI：
10.1016/j.drugalcdep.2014.12.015
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发表时间：
2015-02-01
影响因子：
4.2
通讯作者：
LeSage, Mark G.
中科院分区：
文献类型：
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作者：
Harris, Andrew C.;Tally, Laura;LeSage, Mark G.
背景：需要临床前模型来为食品和药物管理局（FDA）对烟草制品的监管提供信息。通常，烟草成瘾的动物模型涉及单独暴露于尼古丁或尼古丁与分离的烟草成分（如少量生物碱）结合。本研究的目的是建立一个使用含有一系列烟草成分的烟草制品提取物的模型，以更密切地模拟人类接触烟草制品的情况。方法：本研究比较了尼古丁单独和尼古丁剂量当量的无烟烟草水提取物对大鼠颅内自我刺激（ICSS）的成瘾相关影响。提取自Kodiak Wintergreen（一种传统产品）或Camel Snus（一种潜在的“改性风险烟草产品”）。并比较了烟碱提取物与烟碱乙酰胆碱受体（nAChR）不同亚型的结合亲和力。结果：科迪亚克和骆驼鼻烟提取物所含的微量生物碱水平，在分离研究时显示出的增强尼古丁行为效应的范围内。尽管如此，急性注射这两种提取物产生的强化增强（ICSS阈值降低）效果与低至中等尼古丁剂量的尼古丁单独产生的效果相似，也与高剂量尼古丁产生的强化减弱/厌恶（ICSS阈值增加）效果相似。提取物和尼古丁单独在所有研究的nachr上也具有相似的结合亲和力。结论：ICSS测定的相对尼古丁含量是决定科迪亚克和骆驼鼻烟滥用倾向的主要药理学因素。这些模型可用于比较其他烟草制品的相对滥用责任，并可用于模拟fda规定的产品性能标准变化。(C) 2015年由爱思唯尔爱尔兰有限公司出版。
Background: Preclinical models are needed to inform regulation of tobacco products by the Food and Drug Administration (FDA). Typically, animal models of tobacco addiction involve exposure to nicotine alone or nicotine combined with isolated tobacco constituents (e.g. minor alkaloids). The goal of this study was to develop a model using extracts derived from tobacco products that contain a range of tobacco constituents to more closely model product exposure in humans.Methods: This study compared the addiction-related effects of nicotine alone and nicotine dose-equivalent concentrations of aqueous smokeless tobacco extracts on intracranial self-stimulation (ICSS) in rats. Extracts were prepared from Kodiak Wintergreen, a conventional product, or Camel Snus, a potential "modified risk tobacco product". Binding affinities of nicotine alone and extracts at various nicotinic acetylcholine receptor (nAChR) subtypes were also compared.Results: Kodiak and Camel Snus extracts contained levels of minor alkaloids within the range of those shown to enhance nicotine's behavioral effects when studied in isolation. Nonetheless, acute injection of both extracts produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, as well as similar reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at high nicotine doses. Extracts and nicotine alone also had similar binding affinity at all nAChRs studied.Conclusions: Relative nicotine content is the primary pharmacological determinant of the abuse liability of Kodiak and Camel Snus as measured using ICSS. These models may be useful to compare the relative abuse liability of other tobacco products and to model FDA-mandated changes in product performance standards. (C) 2015 Published by Elsevier Ireland Ltd.