Domino Edward F, Hirasawa-Fujita Mika, Ni Lisong, Guthrie Sally K, Zubieta Jon Kar
Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:100-104. doi: 10.1016/j.pnpbp.2015.01.007. Epub 2015 Jan 15.
To determine if overnight tobacco abstinent carriers of the AG or GG (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G polymorphism (rs1799971) differ in [(11)C]carfentanil binding after tobacco smoking.
Twenty healthy American male smokers who abstained from tobacco overnight were genotyped and completed positron emission tomography (PET) scans with the mu opioid receptor agonist, [(11)C]carfentanil. They smoked deniconized (denic) and average nicotine (avnic) cigarettes during the PET scans.
Smoking avnic cigarette decreased the binding potential (BPND) of [(11)C]carfentanil in the right medial prefrontal cortex (mPfc; 6, 56, 18), left anterior medial prefrontal cortex (amPfc; -2, 46, 44), right ventral striatum (vStr; 16, 3, -10), left insula (Ins; -42, 10, -12), right hippocampus (Hippo; 18, -6, -14) and left cerebellum (Cbl; -10, -88, -34), and increased the BPND in left amygdala (Amy; -20, 0, -22), left putamen (Put; -22, 10, -6) and left nucleus accumbens (NAcc; -10, 12, -8). In the AA allele carriers, avnic cigarette smoking significantly changed the BPND compared to after denic smoking in most brain areas listed above. However in the *G carriers the significant BPND changes were confirmed in only amPfc and vStr. Free mu opioid receptor availability was significantly less in the *G than the AA carriers in the Amy and NAcc.
The present study demonstrates that BPND changes induced by avnic smoking in OPRM1 *G carriers were blunted compared to the AA carriers. Also *G smokers had less free mu opioid receptor availability in Amy and NAcc.
确定人类μ阿片受体（OPRM1）A118G多态性（rs1799971）的AG或GG（*G）与AA变异体的过夜戒烟烟草携带者在吸烟后[(11)C]卡芬太尼结合是否存在差异。
对20名过夜戒烟的健康美国男性吸烟者进行基因分型，并用μ阿片受体激动剂[(11)C]卡芬太尼完成正电子发射断层扫描（PET）。他们在PET扫描期间吸食了去尼古丁（denic）香烟和普通尼古丁（avnic）香烟。
吸食avnic香烟降低了[(11)C]卡芬太尼在右侧内侧前额叶皮质（mPfc；6, 56, 18）、左侧前内侧前额叶皮质（amPfc；-2, 46, 44）、右侧腹侧纹状体（vStr；16, 3, -10）、左侧脑岛（Ins；-42, 10, -12）、右侧海马体（Hippo；18, -6, -14）和左侧小脑（Cbl；-10, -88, -34）的结合潜能（BPND），并增加了左侧杏仁核（Amy；-20, 0, -22）、左侧壳核（Put；-22, 10, -6）和左侧伏隔核（NAcc；-10, 12, -8）的BPND。在AA等位基因携带者中，与吸食denic香烟后相比，吸食avnic香烟在上述大多数脑区显著改变了BPND。然而，在*G携带者中，仅在amPfc和vStr中证实了显著的BPND变化。在Amy和NAcc中，*G携带者的游离μ阿片受体可用性显著低于AA携带者。
本研究表明，与AA携带者相比，OPRM1 *G携带者中avnic吸烟诱导的BPND变化减弱。此外，*G吸烟者在Amy和NAcc中的游离μ阿片受体可用性较低。
