Perkins K A, Sanders M, Fonte C, Wilson A S, White W, Stiller R, McNamara D
Department of Psychiatry, University of Pittsburgh, PA 15213, USA.
Psychopharmacology (Berl). 1999 Feb;142(2):158-64. doi: 10.1007/s002130050875.
Nicotine produces interoceptive stimulus effects in humans, which may be critical in understanding tobacco use. It has not yet clearly been demonstrated that discrimination of nicotine, or any drug, in humans is due to its central effects. We compared effects of mecamylamine (10 mg p.o.), a central and peripheral nicotine antagonist, on nicotine discrimination with those of trimethaphan (10-40 microg/kg per min i.v.), a peripheral nicotine antagonist only, and placebo. Smokers (n = 6) were first trained to reliably discriminate 0 versus 20 microg/kg nicotine by nasal spray and then tested on generalization of this discrimination across a range of nicotine doses (0, 3, 6, 12, 20 microg/kg) following antagonist/placebo pretreatment. Nicotine self-administration was also assessed after generalization testing by having participants intermittently choose between nicotine versus placebo spray. Compared with responding following placebo pre-treatment, discrimination of the highest dose of nicotine was significantly attenuated following mecamylamine but not trimethaphan. Similar results were observed for some subjective responses to nicotine. Mecamylamine also tended to increase nicotine self-administration. Consistent with previous animal studies, these results suggest that discriminative stimulus effects of nicotine in humans are mediated at least in part by its central effects.
尼古丁会对人类产生内感受性刺激效应，这可能是理解烟草使用的关键所在。目前尚未明确证实人类对尼古丁或任何药物的辨别是由于其对中枢的作用。我们比较了中枢和外周尼古丁拮抗剂美加明（口服10毫克）、仅外周尼古丁拮抗剂三甲噻方（静脉注射每分钟10 - 40微克/千克）和安慰剂对尼古丁辨别能力的影响。吸烟者（n = 6）首先接受训练，通过鼻腔喷雾可靠地区分0微克/千克与20微克/千克的尼古丁，然后在拮抗剂/安慰剂预处理后，对这一辨别能力在一系列尼古丁剂量（0、3、6、12、20微克/千克）范围内的泛化情况进行测试。在泛化测试后，还通过让参与者在尼古丁喷雾和安慰剂喷雾之间间歇性选择来评估尼古丁的自我给药情况。与安慰剂预处理后的反应相比，美加明预处理后对最高剂量尼古丁的辨别能力显著减弱，而三甲噻方预处理后则没有。在对尼古丁的一些主观反应方面也观察到了类似结果。美加明还倾向于增加尼古丁的自我给药。与先前的动物研究一致，这些结果表明，尼古丁在人类中的辨别性刺激效应至少部分是由其对中枢的作用介导的。
