尼古丁和甲基苯丙胺具有共同的辨别刺激效应。
Nicotine and methamphetamine share discriminative stimulus effects.
作者信息
Gatch Michael B, Flores Elva, Forster Michael J
机构信息
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
出版信息
Drug Alcohol Depend. 2008 Jan 11;93(1-2):63-71. doi: 10.1016/j.drugalcdep.2007.08.020. Epub 2007 Oct 24.
BACKGROUND
Nicotine and methamphetamine are both abused in similar settings, sometimes together. Because there are known interactions between central nicotinic acetylcholine receptors and dopamine receptors, it is of interest to characterize the nature of the interaction of these two compounds in vivo.
METHODS
The purpose of this study was to characterize the extent to which these two compounds produce similar discriminative stimulus effects and to identify pharmacological mechanisms for their interaction. Male Sprague-Dawley rats were trained to discriminate methamphetamine or nicotine from saline. First, the ability of methamphetamine and nicotine to cross-substitute in rats trained to the other compound was tested. Subsequently, the ability of a dopamine antagonist (haloperidol) and a centrally acting nicotinic antagonist (mecamylamine) to block the discriminative stimulus effects of methamphetamine and nicotine were also tested.
RESULTS
Nicotine fully substituted in methamphetamine-trained rats, but methamphetamine only partially substituted in nicotine-trained rats. In nicotine-trained rats, mecamylamine fully antagonized the discriminative stimulus effects of nicotine, but haloperidol had no effect. The partial substitution of methamphetamine was partially attenuated by haloperidol, but not altered by mecamylamine. In methamphetamine-trained rats, mecamylamine failed to antagonize the discriminative stimulus effects of methamphetamine, but haloperidol fully blocked the methamphetamine cue. Mecamylamine blocked the ability of nicotine to substitute for methamphetamine, but haloperidol had no effect.
CONCLUSIONS
These results indicate that nicotine and methamphetamine share discriminative stimulus effects in some subjects and that the two compounds do not act at the same site, but produce their interaction indirectly. These findings suggest that these two compounds might be at least partially interchangeable in human users, and that there are potentially interesting pharmacological reasons for the commonly observed co-administration of nicotine and methamphetamine.
背景
尼古丁和甲基苯丙胺常在相似环境中被滥用，有时还会同时被滥用。由于已知中枢烟碱型乙酰胆碱受体和多巴胺受体之间存在相互作用，因此了解这两种化合物在体内相互作用的性质很有意义。
方法
本研究的目的是确定这两种化合物产生相似辨别刺激效应的程度，并确定它们相互作用的药理学机制。对雄性斯普拉格-道利大鼠进行训练，使其能够区分甲基苯丙胺或尼古丁与生理盐水。首先，测试甲基苯丙胺和尼古丁在经另一种化合物训练的大鼠中交叉替代的能力。随后，还测试了多巴胺拮抗剂（氟哌啶醇）和中枢作用烟碱拮抗剂（美加明）阻断甲基苯丙胺和尼古丁辨别刺激效应的能力。
结果
尼古丁在经甲基苯丙胺训练的大鼠中能完全替代，而甲基苯丙胺在经尼古丁训练的大鼠中只能部分替代。在经尼古丁训练的大鼠中，美加明完全拮抗尼古丁的辨别刺激效应，但氟哌啶醇无效。氟哌啶醇部分减弱了甲基苯丙胺的部分替代作用，但美加明未改变该作用。在经甲基苯丙胺训练的大鼠中，美加明未能拮抗甲基苯丙胺的辨别刺激效应，但氟哌啶醇完全阻断了甲基苯丙胺的提示作用。美加明阻断了尼古丁替代甲基苯丙胺的能力，但氟哌啶醇无效。
结论
这些结果表明，尼古丁和甲基苯丙胺在某些受试者中具有共同的辨别刺激效应，且这两种化合物作用位点不同，而是间接产生相互作用。这些发现表明，这两种化合物在人类使用者中可能至少部分可相互替代，且尼古丁和甲基苯丙胺常见的联合使用可能存在有趣的药理学原因。
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