Nicotine discrimination threshold

Abstract 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. 

Nicotine discrimination behavior, which is mediated by nicotine actions in the CNS, is strongly related to dose, as indicated in tests of generalization across doses (e.g.. Fig. 1), and may be sensitive to very small doses of nicotine (i.e., threshold), below those commonly administered via cigarette smoking. However, it would be a mistake to view any drug discrimination behavior as based solely on the intensity of the interoceptive stimulus effects of that drug. The observed discrimination behavior is... 

Perkins KA, Fonte C, Sanders M, Meeker J, Wilson A (2001c) Threshold doses for nicotine discrimination in smokers and nonsmokers. Psychopharmacology 155 163-170... 

Fig. 2 a Distribution of threshold doses (in Xg kg ) for nicotine nasal spray discrimination in smokers (n = 18) vs. nonsmokers (n = 17). Horizontal lines designate group median thresholds, which did not differ between groups, b Selected subjective responses to nasal spray nicotine doses at, and just below, threshold for discrimination in smokers and nonsmokers. p < 0.05 p < 0.01 for difference between doses. Reprinted from Figs. 1 and 2 in Perkins et al. (2001c) with kind permission from Springer Science and Business Media... 

The median threshold in smokers of 3 p,gkg nicotine is consistent with previous research reporting an ED50 for discrimination (the dose which 50% of subjects can discriminate) of 3 p,gkg in smokers trained to discriminate 12pgkg from placebo (Perkins et al. 1994a). In the current study, the mean blood level of... 

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