Perkins K A, Fonte C, Sanders M, Meeker J, Wilson A
Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15213, USA.
Psychopharmacology (Berl). 2001 May;155(2):163-70. doi: 10.1007/s002130000660.
Tobacco use during initial experimentation often involves modest nicotine exposure, escalating to larger doses and more frequent exposure with the onset of tobacco dependence. Threshold doses for nicotine discrimination therefore may differ between naive and experienced tobacco users.
We determined the lowest (threshold) dose of nasal spray nicotine that smokers and non-smokers could reliably discriminate from placebo spray.
Male and female smokers (n=18) and non-smokers (n=17) were initially trained to discriminate 20 microg/kg from placebo before proceeding to threshold determination sessions, which involved discrimination of progressively lower doses below 20 microg/kg ("descending order" subgroup) or higher doses above 1 microg/kg ("ascending order" subgroup). Threshold was determined by the lowest dose reliably discriminated from placebo (correct on > or =80% of testing trials) and by failure to discriminate the next lowest dose.
Threshold doses for nicotine discrimination were low and not different between smokers and non-smokers (median thresholds of 3 versus 2 microg/kg and approximate blood levels of 2.6 versus 1.6 ng/ml, respectively). Thresholds were similar between descending and ascending order subgroups. Several subjective responses differentiated threshold dose from the dose just below threshold, particularly in non-smokers.
Threshold doses for nasal spray nicotine discrimination in humans are low, well below the typical nicotine delivery of most cigarette brands, and may not change after long-term smoking exposure.
在最初尝试使用烟草期间，尼古丁暴露量通常较小，随着烟草依赖的形成，剂量会逐渐增加且暴露频率更高。因此，初次使用烟草者和有经验的烟草使用者对尼古丁辨别能力的阈值剂量可能有所不同。
我们确定了吸烟者和非吸烟者能够可靠地将其与安慰剂喷雾区分开的最低（阈值）剂量的鼻腔喷雾尼古丁。
男性和女性吸烟者（n = 18）和非吸烟者（n = 17）最初接受训练，以区分20微克/千克与安慰剂，然后进入阈值测定阶段，该阶段涉及区分低于20微克/千克的逐渐降低的剂量（“降序”亚组）或高于1微克/千克的更高剂量（“升序”亚组）。阈值由与安慰剂可靠区分的最低剂量（在≥80%的测试试验中正确）以及无法区分下一个最低剂量来确定。
尼古丁辨别的阈值剂量较低，吸烟者和非吸烟者之间没有差异（中位数阈值分别为3微克/千克和2微克/千克，近似血药浓度分别为2.6纳克/毫升和1.6纳克/毫升）。降序和升序亚组之间的阈值相似。几种主观反应将阈值剂量与刚好低于阈值的剂量区分开来，尤其是在非吸烟者中。
人类鼻腔喷雾尼古丁辨别的阈值剂量较低，远低于大多数香烟品牌的典型尼古丁释放量，并且长期吸烟暴露后可能不会改变。
