Sofuoglu Mehmet, Yoo Sonah, Hill Kevin P, Mooney Marc
Department of Psychiatry, School of Medicine, Yale University, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
Neuropsychopharmacology. 2008 Mar;33(4):715-20. doi: 10.1038/sj.npp.1301460. Epub 2007 May 30.
Although nicotine is the main addictive chemical in tobacco, there have been few studies of pure nicotine self-administration in humans. The goal of this study was to test the parameters of an intravenous (IV) nicotine self-administration model using nicotine doses presumed to be within the range of those of average intake from cigarette smoking. Six male and four female smokers participated in a double-blind, placebo-controlled, crossover study, which consisted of one adaptation and three experimental sessions. In each experimental session, subjects were randomly assigned to one of the three doses of nicotine (0.1, 0.4, or 0.7 mg). The lowest nicotine dose, 0.1 mg, was chosen to be approximately half the amount of nicotine inhaled from one puff of a cigarette. During each experimental session, subjects first sampled the assigned nicotine dose and placebo and then had the opportunity to choose between nicotine and placebo for a total of six choices over a 90-min period. Out of six options, the average (SEM) number of nicotine choices were 3.0 (0.48) for 0.1 mg, 4.7 (0.48) for 0.4 mg and 4.5 (0.46) for 0.7 mg, indicating a significant effect of nicotine dose on nicotine choice. Both the 0.4 and 0.7, but not the 0.1 mg, nicotine doses were preferred to placebo. These higher doses also produced increases in heart rate, blood pressure, and ratings of drug liking and high. Overall, these findings indicate that smokers chose both the 0.4 and the 0.7 mg nicotine doses over placebo. Our model may be useful in the evaluation of the effects of both behavioral and pharmacological manipulations on nicotine self-administration in humans.
尽管尼古丁是烟草中的主要成瘾性化学物质，但针对人类纯尼古丁自我给药的研究却很少。本研究的目的是使用假定在吸烟平均摄入量范围内的尼古丁剂量，测试静脉注射（IV）尼古丁自我给药模型的参数。六名男性和四名女性吸烟者参与了一项双盲、安慰剂对照的交叉研究，该研究包括一个适应期和三个实验阶段。在每个实验阶段，受试者被随机分配到三种尼古丁剂量（0.1、0.4或0.7毫克）之一。最低的尼古丁剂量0.1毫克被选定为大约是吸一口香烟所吸入尼古丁量的一半。在每个实验阶段，受试者首先对分配的尼古丁剂量和安慰剂进行采样，然后有机会在尼古丁和安慰剂之间进行选择，在90分钟内总共进行六次选择。在六个选项中，0.1毫克尼古丁的平均（标准误）选择次数为3.0（0.48），0.4毫克为4.7（0.48），0.7毫克为4.5（0.46），表明尼古丁剂量对尼古丁选择有显著影响。0.4毫克和0.7毫克的尼古丁剂量均比安慰剂更受青睐。这些较高的剂量还导致心率、血压以及对药物喜好和兴奋程度的评分增加。总体而言，这些发现表明吸烟者在安慰剂之上选择了0.4毫克和0.7毫克的尼古丁剂量。我们的模型可能有助于评估行为和药理学操作对人类尼古丁自我给药的影响。
