Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers
Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers
复制标题
DOI：
10.1073/pnas.1018699108
复制
发表时间：
2011-05-31
影响因子：
11.1
通讯作者：
Lerman, Caryn
中科院分区：
文献类型：
--
作者：
Ray, Riju;Ruparel, Kosha;Lerman, Caryn
有证据表明，内源性阿片系统，特别是μ阿片受体（莫尔）介导了包括尼古丁在内的滥用药物的奖励效应。人类莫尔基因（OPRM 1 A118 G）中的单核苷酸多态性（SNP）已显示可改变临床前模型中的受体蛋白水平和人类的吸烟行为。为了阐明这些关联的潜在机制，我们进行了OPRM 1 A118 G基因型对莫尔结合潜力（BPND或受体可用性）影响的体内研究。22名预先筛选基因型（12 A/A，10 */G）的吸烟者在整夜戒烟并暴露于含尼古丁香烟和脱尼古丁香烟后完成了两次[C-11]卡芬太尼正电子发射断层扫描（PET）成像。独立的会话，吸烟者纯合子野生型OPRM 1 A等位基因表现出显着更高的水平莫尔BPND比吸烟者携带G等位基因在双侧杏仁核，左丘脑，左前扣带皮层。在G等位基因携带者中，主观奖励差异（去尼古丁香烟与尼古丁香烟）的程度与右杏仁核、尾状核、前扣带皮层和丘脑的莫尔BPND差异显著相关。未来的翻译研究可以阐明MORs在尼古丁成瘾中的作用，这可能会导致新的治疗方法的开发。
Evidence points to the endogenous opioid system, and the mu-opioid receptor (MOR) in particular, in mediating the rewarding effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the human MOR gene (OPRM1 A118G) has been shown to alter receptor protein level in preclinical models and smoking behavior in humans. To clarify the underlying mechanisms for these associations, we conducted an in vivo investigation of the effects of OPRM1 A118G genotype on MOR binding potential (BPND or receptor availability). Twenty-two smokers prescreened for genotype (12 A/A, 10 */G) completed two [C-11]carfentanil positron emission tomography (PET) imaging sessions following overnight abstinence and exposure to a nicotine-containing cigarette and a denicotinized cigarette. Independent of session, smokers homozygous for the wild-type OPRM1 A allele exhibited significantly higher levels of MOR BPND than smokers carrying the G allele in bilateral amygdala, left thalamus, and left anterior cingulate cortex. Among G allele carriers, the extent of subjective reward difference (denicotinized versus nicotine cigarette) was associated significantly with MOR BPND difference in right amygdala, caudate, anterior cingulate cortex, and thalamus. Future translational investigations can elucidate the role of MORs in nicotine addiction, which may lead to development of novel therapeutics.