Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers

Abstract.Rationale: When administered acutely to nonsmokers, nicotine's effects on performance are inconsistent, perhaps because of suboptimal dosing or initial dysphoria that could interfere with performance. Objective: The purpose of this study was to determine if a range of nicotine doses administered for 8 days to nonsmokers would enhance psychomotor and cognitive abilities and to document the development of nicotine tolerance or sensitization. Methods: Twelve male volunteers, who reported ever smoking five cigarettes or less, participated in 8 consecutive experimental days in which they were administered four doses of nicotine polacrilex gum each day in this order: 0, 2, 4, and 8 mg. Performance, subjective, and physiological measures were assessed before and after each dose. Results: Plasma nicotine concentration ranged from 6.9 to 11.5 ng/ml following the 8 mg dose. Nicotine increased rate of responding and decreased response time on working memory (digit recall); however, accuracy was impaired. Nicotine also decreased accuracy on visual scanning and attention (two-letter search), and the 8 mg dose impaired gross motor coordination (circular lights). Tolerance did not develop to the performance impairing effects of nicotine. Nicotine produced dose-related increases in ratings of dysphoria and negative mood, including tension, anxiety, nervousness, turning of stomach, and sedation. Tolerance developed to some, but not all, of these aversive effects. Tolerance also was not observed to the increased cardiovascular measures. Conclusion: Although tolerance developed to some of the aversive effects of nicotine, performance enhancement was not observed. These data do not support the hypothesis that nicotine-induced performance enhancement contributes to the reinforcing effects of tobacco use during the early stages of dependence development.