According to the Pavlovian conditioning model, drug tolerance is modulated by drug-associated environmental cues. This study evaluated the contribution of drug-associated cues in the development of cross-tolerance to the tachycardic effects of nicotine from tobacco and alcohol in human subjects. Forty undergraduate students were recruited for this experiment, and each student was randomly assigned to one of two experimental conditions. Twenty students smoked nicotine-containing cigarettes in context A and placebo cigarettes in context B, and twenty students smoked nicotine-containing cigarettes in context B and placebo cigarettes in context A. A cross-tolerance test was carried out by dividing the subjects in each condition into two subgroups (n = 10). Each subgroup consumed alcohol in both contexts (A and B). The results of this experiment showed that cross-tolerance between nicotine and alcohol was exhibited only if the cross-tolerance test was carried out in the same context where tolerance had developed to the nicotine from tobacco. These results support the hypothesis that drug-associated environmental stimuli play a modulatory role in the development of cross-tolerance between nicotine from tobacco and alcohol.
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