Addictions Division, Centre for Addiction and Mental Health, Toronto, Canada.
Campbell Family Mental Health Research Institute Toronto, Canada.
Int J Neuropsychopharmacol. 2018 Jun 1;21(6):503-512. doi: 10.1093/ijnp/pyx119.
Identifying the biological basis of smoking cessation success is of growing interest. The rate of nicotine metabolism, measured by the nicotine metabolite ratio, affects multiple aspects of nicotine dependence. Fast nicotine metabolizers tend to smoke more, experience more withdrawal and craving, and have lower cessation rates compared with slow metabolizers. The nicotine metabolite ratio predicts treatment response, and differences in brain activation between fast metabolizers and slow metabolizers have been reported in fMRI studies. As reinforcing/rewarding effects of tobacco are associated with dopamine transmission, the purpose of the present study was to study the dopaminergic system in human smokers based on their nicotine metabolite ratio.
The first aim of the study was to explore if there were differences in D2 and D3 receptor binding between fast metabolizers and slow metabolizers during abstinence. The second aim was to explore smoking-induced dopamine release in both groups. Participants underwent 2 [11C]-(+)-PHNO PET scans: one scan during abstinence and the other after smoking a tobacco cigarette. Subjective measures were recorded and blood was drawn for measurement of nicotine and cotinine levels.
During abstinence, slow metabolizers (n = 13) had lower [11C]-(+)-PHNO binding potential than fast metabolizers (n = 15) restricted to the D2 regions of the associative striatum and sensorimotor striatum. After smoking a cigarette, [11C]-(+)-PHNO binding potential was decreased in the limbic striatum and ventral pallidum, suggestive of increases in dopamine, but there were no nicotine metabolite ratio differences.
Further studies are required to delineate if differences in [11C]-(+)-PHNO binding between slow metabolizers and fast metabolizers at abstinence baseline are preexisting traits or induced by prolonged tobacco use.
识别戒烟成功的生物学基础越来越受到关注。尼古丁代谢率，通过尼古丁代谢物比值来衡量，影响尼古丁依赖的多个方面。与慢代谢者相比，快代谢者吸烟更多，经历更多的戒断和渴望，戒烟率更低。尼古丁代谢物比值预测治疗反应，并且在 fMRI 研究中已经报道了快代谢者和慢代谢者之间大脑激活的差异。由于烟草的强化/奖励作用与多巴胺传递有关，本研究的目的是根据尼古丁代谢物比值研究人类吸烟者的多巴胺系统。
研究的第一个目的是探索在戒断期间，快代谢者和慢代谢者之间的 D2 和 D3 受体结合是否存在差异。第二个目的是探索两组吸烟引起的多巴胺释放。参与者接受了 2 次 [11C]-(+)-PHNO PET 扫描：一次在戒断期间，另一次在吸烟一支香烟后。记录主观测量值并采血以测量尼古丁和可替宁水平。
在戒断期间，与快代谢者（n = 15）相比，慢代谢者（n = 13）在联合纹状体和感觉运动纹状体的 D2 区域的 [11C]-(+)-PHNO 结合潜能较低。吸烟一支香烟后，边缘纹状体和腹侧苍白球中的 [11C]-(+)-PHNO 结合潜能降低，提示多巴胺增加，但尼古丁代谢物比值没有差异。
需要进一步研究以阐明在戒断基线时慢代谢者和快代谢者之间 [11C]-(+)-PHNO 结合的差异是先天特征还是由长期吸烟引起的。
