Discriminative stimulus properties of nicotine at low doses: the effects of caffeine preload

Discriminative stimulus properties of low nicotine doses administered in the form of chewing gum in combination with caffeine have been evaluated in humans, using established behavioural drug discrimination procedures. Twenty-one smokers who were also regular coffee drinkers were trained to discriminate 0 versus 1 mg nicotine chewing gum. Twenty subjects (11 men and nine women) were able to reach criterion performance (at least 80% correct). Generalization of responding across nicotine doses of 0, 0.25, 0.5 and 1 mg was then examined. Subjects were randomly allocated to receive either 50 mg caffeine or placebo before testing. Nicotine-appropriate responding was linearly related to dose, demonstrating that smokers can accurately discriminate nicotine from placebo and between relatively small doses of nicotine. Nicotine-appropriate responding was high at the 0 mg nicotine dose in the caffeine group demonstrating a partial generalization. Subjective effects assessed concurrently with behavioural discrimination revealed that nicotine discrimination was guided by the interoceptive cues of 'sensations in mouth', 'taste', 'heart rate', 'stimulated', 'alert' 'jittery' and 'nausea'. Caffeine increased self-ratings of 'stimulated' and 'alert' (at the 0 mg nicotine dose) and 'jittery' at the 0.5 and 1.0 mg nicotine dose. Relationships between nicotine-appropriate responding and subjective feelings induced by caffeine suggested that feelings of 'stimulated' and 'alert' were guiding discrimination behaviour. These data are discussed in terms of interoceptive nicotine cues and their importance at different doses and after caffeine preload.