Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response.
Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response.
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DOI：
10.1093/ntr/ntac026
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发表时间：
2022-10-17
影响因子：
4.7
通讯作者：
Morris, Evan D.
中科院分区：
文献类型：
--
作者：
Zakiniaeiz, Yasmin;Liu, Heather;Gao, Hong;Najafzadeh, Soheila;Ropchan, Jim;Nabulsi, Nabeel;Huang, Yiyun;Matuskey, David;Chen, Ming-Kai;Cosgrove, Kelly P.;Morris, Evan D.
吸烟是一个主要的公共卫生负担。吸烟的一线药物治疗是尼古丁替代疗法（如尼古丁贴片（NIC））。尼古丁作用于多巴胺末梢上的烟碱-乙酰胆碱受体，在腹侧和背侧纹状体释放多巴胺，分别编码奖赏和习惯形成。为了更好地理解治疗效果，使用了与动力学模型相结合的自然主义实验设计，该动力学模型旨在表征吸烟诱导的体内多巴胺释放。35名吸烟者（16名女性）以随机、平衡顺序贴敷NIC（21 mg，每日一次）1周和安慰剂贴剂（PBO）1周。在NIC下1周后，然后整夜戒烟，吸烟者参加了90分钟的[11 C]雷氯必利正电子发射断层扫描，并在扫描仪中吸烟。PBO扫描遵循相同的程序。在体素水平上使用时变动力学模型来模拟在刺激开始时瞬时达到峰值并指数衰减的瞬时多巴胺释放。多巴胺释放的幅度和空间范围进行了估计。吸烟者根据尼古丁依赖水平和尼古丁代谢率进行细分。多巴胺的释放幅度增强NIC在腹侧纹状体和减少NIC在背侧纹状体。在这两种情况下，依赖性更强的吸烟者比依赖性更弱的吸烟者激活了更多的体素。在PBO下，快代谢者比慢代谢者激活腹侧纹状体更多的体素和背侧纹状体更少的体素。这些发现表明，该模型捕获了对吸烟的短暂多巴胺反应的模式，这在吸烟者亚组分类中可能是不同的。这是第一项研究表明，NIC改变了吸烟诱导的多巴胺释放的高度局部模式，尼古丁依赖水平和尼古丁清除率有助于这些改变。目前的工作包括一个同质的受试者样本的人口统计学和吸烟变量，以及一个高度敏感的模型，能够检测到显着的急性多巴胺瞬变。这项研究的结果为最近确定的用于预测尼古丁替代疗法对多巴胺功能影响的生物标志物提供了支持，这可能有助于完善戒烟的临床实践。
Tobacco smoking is a major public health burden. The first-line pharmacological treatment for tobacco smoking is nicotine replacement therapy (eg, the nicotine patch (NIC)). Nicotine acts on nicotinic-acetylcholine receptors on dopamine terminals to release dopamine in the ventral and dorsal striatum encoding reward and habit formation, respectively. To better understand treatment efficacy, a naturalistic experimental design combined with a kinetic model designed to characterize smoking-induced dopamine release in vivo was used. Thirty-five tobacco smokers (16 female) wore a NIC (21 mg, daily) for 1-week and a placebo patch (PBO) for 1-week in a randomized, counter-balanced order. Following 1-week under NIC and then overnight abstinence, smokers participated in a 90-minute [11C]raclopride positron emission tomography scan and smoked a cigarette while in the scanner. Identical procedures were followed for the PBO scan. A time-varying kinetic model was used at the voxel level to model transient dopamine release peaking instantaneously at the start of the stimulus and decaying exponentially. Magnitude and spatial extent of dopamine release were estimated. Smokers were subcategorized by nicotine dependence level and nicotine metabolism rate. Dopamine release magnitude was enhanced by NIC in ventral striatum and diminished by NIC in dorsal striatum. More-dependent smokers activated more voxels than the less-dependent smokers under both conditions. Under PBO, fast metabolizers activated more voxels in ventral striatum and fewer voxels in dorsal striatum compared to slow metabolizers. These findings demonstrate that the model captured a pattern of transient dopamine responses to cigarette smoking which may be different across smoker subgroup categorizations. This is the first study to show that NIC alters highly localized patterns of cigarette smoking-induced dopamine release and that levels of nicotine dependence and nicotine clearance rate contribute to these alterations. This current work included a homogeneous subject sample with regards to demographic and smoking variables, as well as a highly sensitive model capable of detecting significant acute dopamine transients. The findings of this study add support to the recent identification of biomarkers for predicting the effect of nicotine replacement therapies on dopamine function which could help refine clinical practice for smoking cessation.
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影响因子：
4.7
作者：
Domino, Edward F.;Ni, Lisong;Zubieta, Jon-Kar
通讯作者：
Zubieta, Jon-Kar
影响因子：
5.3
作者：
Cosgrove, Kelly P.;Wang, Shuo;Morris, Evan D.
通讯作者：
Morris, Evan D.
影响因子：
6.8
作者：
AKAIKE, H
通讯作者：
AKAIKE, H
影响因子：
7.3
作者：
BENWELL, MEM;BALFOUR, DJK;BIRRELL, CE
通讯作者：
BIRRELL, CE
影响因子：
4.8
作者：
Kim, Su Jin;Sullivan, Jenna M.;Wang, Shuo;Cosgrove, Kelly P.;Morris, Evan D.
通讯作者：
Morris, Evan D.