吸烟者尼古丁代谢率对吸烟者[11C]-(+)-PHNO PET结合能力的影响
2018/03/19
摘要
背景：明确戒烟成功的生物学评价标准成为研究热点。尼古丁代谢通过代谢率（NMR）进行评价，也反映了尼古丁依赖的多种形式。相比较尼古丁缓慢代谢者（SM）,尼古丁快速代谢者（FM）吸烟量更大，戒断症状更明显，戒断率更低。NMR可以用于预测治疗反馈，FM和SM大脑活动差异也在fMR研究中得到证实。作为烟草增强/奖励作用与多巴胺（DA）传递相关，本研究目的旨在根据NMR研究吸烟者多巴胺能系统。
方法：本研究首要目的在于探究戒断期间FM和SM之间D2和D3受体之间结合差异。次要目的在于评价两组吸烟诱导DA释放情况。受试者接受2 [11C]-(+)-PHNO PET扫描：戒断期进行一次扫描；另一次扫描在抽一根烟后。记录主观测定结果并测定血清尼古丁和可替宁水平。结果：戒断期，在联合纹状体和感觉运动纹状体限定D2区域，SM组(n=13) [11C]-(+)-PHNO结合能力(BPND)逊于FM 组(n=15)。在吸一支烟以后，[11C]-(+)-PHNO BPND在边缘纹状体和腹侧苍白球下降，提示DA中增加，但NMR并无差异。
结论：需要进一步研究明确戒烟阶段基线SM和FM之间的差异，以明确差异是预先存在还是长期吸烟导致。
Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET binding in Tobacco Smokers.
Di Ciano P.
Abstract
BACKGROUND:Identifying the biological basis of smoking cessation success is of growing interest. The rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), affects multiple aspects of nicotine dependence. Fast nicotine metabolizers (FM) tend to smoke more, experience more withdrawal and craving and have lower cessation rates as compared to slow metabolizers (SM). The NMR predicts treatment response, and differences in brain activation between FM and SM have been reported in fMRI studies. As reinforcing/rewarding effects of tobacco are associated with dopamine (DA) transmission, the purpose of the present study was to study the dopaminergic system in human smokers based on their NMR.
METHODS:The first aim of the study was to explore if there were differences in D2 and D3 receptor binding between FMs and SMs during abstinence. The second aim was to explore smoking-induced DA 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.
RESULTS:During abstinence, SMs (n=13) had lower [11C]-(+)-PHNO binding potential (BPND) than FM (n=15) restricted to the D2 regions of the associative striatum and sensorimotor striatum. After smoking a cigarette, [11C]-(+)-PHNO BPND was decreased in the limbic striatum and ventral pallidum, suggestive of increases in DA, but there were no NMR differences.
CONCLUSIONS:Further studies are required to delineate if differences in [11C]-(+)-PHNO binding between SM and FM at abstinence baseline are pre-existing traits or induced by prolonged tobacco use.
背景：明确戒烟成功的生物学评价标准成为研究热点。尼古丁代谢通过代谢率（NMR）进行评价，也反映了尼古丁依赖的多种形式。相比较尼古丁缓慢代谢者（SM）,尼古丁快速代谢者（FM）吸烟量更大，戒断症状更明显，戒断率更低。NMR可以用于预测治疗反馈，FM和SM大脑活动差异也在fMR研究中得到证实。作为烟草增强/奖励作用与多巴胺（DA）传递相关，本研究目的旨在根据NMR研究吸烟者多巴胺能系统。
方法：本研究首要目的在于探究戒断期间FM和SM之间D2和D3受体之间结合差异。次要目的在于评价两组吸烟诱导DA释放情况。受试者接受2 [11C]-(+)-PHNO PET扫描：戒断期进行一次扫描；另一次扫描在抽一根烟后。记录主观测定结果并测定血清尼古丁和可替宁水平。结果：戒断期，在联合纹状体和感觉运动纹状体限定D2区域，SM组(n=13) [11C]-(+)-PHNO结合能力(BPND)逊于FM 组(n=15)。在吸一支烟以后，[11C]-(+)-PHNO BPND在边缘纹状体和腹侧苍白球下降，提示DA中增加，但NMR并无差异。
结论：需要进一步研究明确戒烟阶段基线SM和FM之间的差异，以明确差异是预先存在还是长期吸烟导致。
上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译）
（Int J Neuropsychopharmacol. 2018 Jan 13.）
（Int J Neuropsychopharmacol. 2018 Jan 13.）
Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET binding in Tobacco Smokers.
Di Ciano P.
Abstract
BACKGROUND:Identifying the biological basis of smoking cessation success is of growing interest. The rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), affects multiple aspects of nicotine dependence. Fast nicotine metabolizers (FM) tend to smoke more, experience more withdrawal and craving and have lower cessation rates as compared to slow metabolizers (SM). The NMR predicts treatment response, and differences in brain activation between FM and SM have been reported in fMRI studies. As reinforcing/rewarding effects of tobacco are associated with dopamine (DA) transmission, the purpose of the present study was to study the dopaminergic system in human smokers based on their NMR.
METHODS:The first aim of the study was to explore if there were differences in D2 and D3 receptor binding between FMs and SMs during abstinence. The second aim was to explore smoking-induced DA 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.
RESULTS:During abstinence, SMs (n=13) had lower [11C]-(+)-PHNO binding potential (BPND) than FM (n=15) restricted to the D2 regions of the associative striatum and sensorimotor striatum. After smoking a cigarette, [11C]-(+)-PHNO BPND was decreased in the limbic striatum and ventral pallidum, suggestive of increases in DA, but there were no NMR differences.
CONCLUSIONS:Further studies are required to delineate if differences in [11C]-(+)-PHNO binding between SM and FM at abstinence baseline are pre-existing traits or induced by prolonged tobacco use.
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