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首页> 外文期刊>Behavioural pharmacology >The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment.
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The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment.

机译：尼古丁预处理后对人的歧视性刺激和增强作用。

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Smokers often report that the first cigarette of the day is the most rewarding, and subsequent smoking is less rewarding. Reduction in smoking enjoyment later in the day may be related to acute tolerance to the discriminative stimulus effects of nicotine. We examined changes in nicotine discrimination behaviour in humans as a function of acute nicotine pretreatment. Male and female dependent smokers (n = 15) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) without nicotine pretreatment. They then were tested on generalization of discrimination across a range of spray doses from 0-20 microg/kg following pretreatment with placebo, moderate dose (14-21 mg) or high dose (28-42 mg) transdermal nicotine. Generalization testing involved both two- and three-response ('novel' option) quantitative procedures. Subjects also engaged in a self-administration phase at the end of each session, involving choices between nicotine (20 microg/kg) and placebo spray. Nicotine pretreatment significantly attenuated nicotine-appropriate responding at higher nicotine spray doses, suggesting acute tolerance, but only in women. Similar results were seen for subjective 'head rush', suggesting this effect may be related to discrimination behaviour in women. However, nicotine pretreatment also increased novel-appropriate responding, especially in men, following intermediate generalization doses, suggesting qualitatively different stimulus effects. Although differences were not significant, nicotine self-administration tended to be inversely associated with nicotine pretreatment dose in men but not in women. These results only modestly support the notion of acute tolerance to the discriminative stimulus effects of nicotine, and even then only in women and not in men.
机译：吸烟者经常报告说，一天的第一支香烟最有好处，而随后吸烟则没有那么多好处。当天晚些时候吸烟量的减少可能与对尼古丁的歧视性刺激作用的急性耐受有关。我们检查了作为急性尼古丁预处理功能的人类中尼古丁歧视行为的变化。男性和女性吸烟者（n = 15）最初经过培训，可以通过鼻喷雾剂从安慰剂（0 microg / kg）中区分出20 microg / kg尼古丁，而无需尼古丁预处理。然后，在对安慰剂，中剂量（14-21 mg）或高剂量（28-42 mg）经皮尼古丁进行预处理后，在0-20 microg / kg的一系列喷雾剂量下对他们的辨别能力进行测试。泛化测试涉及两个和三个响应（“新颖”选项）定量程序。在每节课结束时，受试者还处于自我给药阶段，涉及尼古丁（20微克/千克）和安慰剂喷雾之间的选择。尼古丁预处理在较高的尼古丁喷雾剂量下能显着减弱适当的尼古丁反应，表明具有急性耐受性，但仅在女性中。对于主观的“头部急促”也观察到了类似的结果，表明这种效应可能与女性的歧视行为有关。但是，尼古丁预处理还可以增加中等反应，尤其是在男性患者中，随后进行中等剂量的尼古丁预处理，表明其刺激效果在质上有所不同。尽管差异并不显着，但在男性中尼古丁自我给药与尼古丁预处理剂量呈负相关，而在女性中则没有。这些结果仅适度地支持了对尼古丁的歧视性刺激作用的急性耐受性的观念，甚至在女性中而不是男性中。

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