Perkins K A, Epstein L H, Stiller R L, Marks B L, Jacob R G
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, PA 15213.
Psychopharmacology (Berl). 1989;97(4):529-34. doi: 10.1007/BF00439559.
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.
对尼古丁作用的耐受性反映了生理适应性，可能与吸烟行为的发展和持续存在有关。然而，关于人类对尼古丁的耐受性知之甚少，部分原因是方法上存在困难。本研究采用定量鼻腔喷雾尼古丁程序，研究了尼古丁对心率（HR）影响的慢性和急性耐受性。八名“轻度”吸烟者（每天少于20支香烟）和十名“重度”吸烟者（每天大于或等于20支）在不同的日子参加了两个实验环节，在每个环节中，他们接受四次高尼古丁剂量（每公斤体重15微克，相当于一支典型香烟）或低尼古丁剂量（7.5微克/公斤）的给药（每20分钟一次），同时在每次给药后的5分钟内监测心率。与轻度吸烟者相比，重度吸烟者对高剂量的心率反应明显较小，表明其具有更高的慢性耐受性，但两组对低剂量的反应没有差异。两种剂量在四个5分钟时间段内均未观察到对心率反应的急性耐受性。然而，随后对每次给药后前2分钟内心率反应的检查确实表明存在急性耐受性，特别是对于低剂量，因为这种更急性的心率反应从第一次给药到最后一次给药逐渐下降。这些结果证明了对尼古丁心率影响的慢性耐受性，在较小程度上也证明了急性耐受性，并表明两者可能都与剂量有关。
