Acute tolerance to nicotine in smokers: lack of dissipation within 2 hours

Greater understanding of development and dissipation of acute tolerance to nicotine may help explain temporal patterns of nicotine self-administration in smokers. The time course of dissipation of acute tolerance to nicotine was examined in 16 smokers (8M, 8F) participating in four sessions differing on pretreatment exposure or time interval prior to nicotine (20 micrograms/kg) challenge: placebo 30 min before, or nicotine (20 micrograms/kg) 30, 60, or 120 min before challenge. Nicotine and placebo were administered by measured-dose nasal spray. The measurement battery consisted of subjective, cardiovascular, thermal pain detection, and behavioral performance measures. Results demonstrated significant acute tolerance (i.e. smaller responses to nicotine challenge following nicotine versus placebo pretreatment) for most subjective measures and for heart rate. Acute tolerance dissipated with lengthening inter-dose interval for two subjective measures, dose strength and arousal, but there was no tolerance dissipation for other measures. In contrast, nicotine pretreatment resulted in acute sensitization of finger temperature (vasoconstriction) response, which dissipated with lengthening interval. No acute tolerance was observed for thermal pain detection or performance measures. These findings demonstrate that acute tolerance develops quickly to some subjective and cardiovascular effects of nicotine. However, acute tolerance to most effects did not dissipate over 2 h, suggesting that, following acute tolerance development during initial exposure, most smokers generally obtain similar magnitude of effects from each subsequent nicotine exposure (i.e. cigarettes smoked later in the day).