Chronic and acute tolerance to the heart rate effects of nicotine.

Tolerance to the effects of nicotine reflects physiological adaptation and may be related to the development and persistence of smoking behavior. However, little is known about tolerance to nicotine in humans, in part due to methodological difficulties. This study examined chronic and acute tolerance to nicotine's effect on heart rate (HR) using a measured-dose nasal spray nicotine procedure. Eight "Light" smokers (less than 20 cigarettes per day) and ten "Heavy" smokers (greater than or equal to 20 per day) participated in two sessions on separate days in which they received four administrations (1 every 20 min) of a high nicotine dose (15 micrograms per kg body weight, equivalent to a typical cigarette) or a low nicotine dose (7.5 micrograms/kg) while HR was monitored during the 5 min following each administration. Compared with Light smokers, Heavy smokers had significantly smaller HR responses to the high dose, indicating greater chronic tolerance, but there was no difference between groups in response to the low dose. Acute tolerance to HR response across the four 5-min periods was not observed with either dose. However, subsequent examination of HR response in the first 2 min following each dose administration did suggest acute tolerance, particularly for the low dose, as this more acute HR response declined from the first to the last administration. These results demonstrate chronic and, to a lesser extent, acute tolerance to HR effects of nicotine and suggest that both may be dose dependent.