title: Tobacco smoking produces greater striatal dopamine release in G-allele carriers with mu opioid receptor A118G polymorphism.
abstract: OBJECTIVE
  To determine if carriers of the allelic expression of the G variant of the human mu opioid receptor (OPRM1) A118G polymorphism have greater increases in striatal dopamine (DA) release after tobacco smoking.
  
  
  METHODS
  Nineteen of 20 genotyped male tobacco smokers, after overnight abstinence, smoked denicotinized (denic) and average nicotine (nic) containing tobacco cigarettes in a PET brain imaging study using [(11)C]raclopride.
  
  
  RESULTS
  The right striatum had more free D(2) receptors than the left striatum pre- and post-tobacco smoking. After smoking the nic cigarettes, mean decreased DA binding was observed in the left dorsal caudate (-14 6 11; t=3.77), left and right ventral putamen (-26 3-8; t=4.27; 28 2 1; t=4.25, respectively), and right caudate (17 18 1; t=3.92). The effects of A118G genotype on the binding potentials for these four regions were then analyzed. Carriers of the G allele had larger magnitudes of DA release in response to nic smoking than those homozygous for the more prevalent AA allele in the right caudate and right ventral pallidum (t=3.03; p=0.008 and t=3.91; p=0.001). A voxel by voxel whole brain SPM analysis using an independent samples t test did not reveal any other differences between genotype groups. In addition, the venous plasma cortisol levels of the volunteers from 8:30 a.m. to 12:40 p.m. were lower in the AG/GG allele carriers. Nic smoking increased plasma cortisol in both groups, but they were higher in the AA group.
  
  
  CONCLUSIONS
  This preliminary study indicates a difference in both brain striatal DA release and plasma cortisol in A118G polymorphic male tobacco smokers.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109-5632, USA. efdabcde@umich.edu
authors.forename: Edward F
authors.initials: EF
authors.lastname: Domino
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Evans
authors.forename: Lisong
authors.initials: L
authors.lastname: Ni
authors.forename: Sally K
authors.initials: SK
authors.lastname: Guthrie
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000483:Alleles; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011877:Radionuclide Imaging; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000235:genetics* / Q000378:metabolism
chemical_list: D017450:Receptors, Opioid, mu; D004298:Dopamine; D006854:Hydrocortisone