Perkins Kenneth A
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
Handb Exp Pharmacol. 2009(192):369-400. doi: 10.1007/978-3-540-69248-5_13.
Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. Men may be more sensitive than women to nicotine's discriminative stimulus effects, consistent with other research suggesting that nicotine is more reinforcing in men than in women. Other potential individual differences in nicotine discrimination have not been clearly tested, but may include genetics, obesity, and dependence on other drugs. Acute environmental factors that alter nicotine discrimination include the specific training and testing conditions, pointing to the need for careful control over such conditions during research. Other factors, such as concurrent acute use of alcohol or caffeine, do not appear to alter nicotine discrimination, suggesting that changes in nicotine discrimination are not likely explanations for the association of smoking behavior with use of those drugs. Concurrent physical activity also does not appear to alter nicotine discrimination, indicating that results from studies of discrimination in subjects at quiet rest, the standard approach in this research, generalize well to discrimination in subjects engaged in various activities, as often occurs in the natural environment. Future research should more clearly examine the potential role of nicotine's discriminative stimulus effects in nicotine reinforcement and determine the generalizability of these findings to nicotine delivered by other means, particularly tobacco smoking.
行为辨别程序清楚地表明，尼古丁会在人类身上引发内感受性刺激效应，这些效应可通过各种药理学操作以及一些行为操作进行调节。本章讨论了尼古丁辨别参数以及可能改变辨别行为的慢性和急性因素，重点介绍了作者关于通过鼻喷雾剂递送尼古丁的研究。人类对尼古丁的辨别是由中枢介导的，因为中枢和外周尼古丁拮抗剂美加明会阻断辨别，但外周拮抗剂三甲噻方则不会。通过喷雾剂辨别尼古丁的阈剂量在吸烟者和非吸烟者中似乎都非常低。由于吸烟烟草比喷雾剂更快地递送尼古丁，通过吸烟摄入尼古丁的阈剂量可能更低。就个体差异而言，吸烟者可能会对较高剂量尼古丁的辨别刺激效应产生耐受性，但对低剂量则不会。男性可能比女性对尼古丁的辨别刺激效应更敏感，这与其他研究结果一致，即尼古丁对男性的强化作用比对女性更强。尼古丁辨别方面其他潜在的个体差异尚未得到明确测试，但可能包括基因、肥胖以及对其他药物的依赖。改变尼古丁辨别的急性环境因素包括特定的训练和测试条件，这表明在研究过程中需要仔细控制这些条件。其他因素，如同时急性使用酒精或咖啡因，似乎不会改变尼古丁辨别，这表明尼古丁辨别变化不太可能是吸烟行为与使用这些药物之间关联的原因。同时进行体育活动似乎也不会改变尼古丁辨别，这表明在安静休息状态下的受试者中进行辨别研究（本研究中的标准方法）的结果能够很好地推广到从事各种活动的受试者中的辨别情况，而这在自然环境中经常发生。未来的研究应该更清楚地研究尼古丁辨别刺激效应在尼古丁强化中的潜在作用，并确定这些发现对通过其他方式递送的尼古丁（特别是吸烟）的可推广性。
