title: Regional brain [(11)C]carfentanil binding following tobacco smoking.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA. Electronic address: efdabcde@umich.edu.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Domino
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Mika
authors.initials: M
authors.lastname: Hirasawa-Fujita
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lisong
authors.initials: L
authors.lastname: Ni
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sally K
authors.initials: SK
authors.lastname: Guthrie
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jon Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007839:Functional Laterality; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D012907:Smoking / Q000235:genetics / Q000473:pathology*
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; C017114:carfentanil; D005283:Fentanyl
keywords: A118G; OPRM1; PET; Smoking; [(11)C]carfentanil