title: Smoking modulation of mu-opioid and dopamine D2 receptor-mediated neurotransmission in humans.
abstract: This is a pilot examination of the hypothesis that some of the effects of smoking cigarettes in humans are mediated through nicotine activation of opioid and dopamine (DA) neurotransmission. Neuroimaging was performed using positron emission tomography and the radiotracers [11C]carfentanil and [11C]raclopride, labeling mu-opioid and DA D2 receptors, respectively. Six healthy male smokers were abstinent overnight. After radiotracer administration, subjects smoked two denicotinized cigarettes, followed 45 min later by two average nicotine cigarettes. Dynamic data were acquired over 90 min, and transformed into parametric maps of receptor availability in vivo (binding potential, BP), corresponding to low and high nicotine smoking periods and analyzed on a voxel-by-voxel basis using SPM'99 and correction for multiple comparisons. Significant activation of mu-opioid receptor-mediated neurotransmission from denicotinized to average nicotine conditions was observed in the right anterior cingulate cortex. DA D2 neurotransmission was activated in the ventral basal ganglia, correlating with Fagerström scale nicotine dependence scores. Lower mu-opioid receptor BP was also detected during the denicotinized smoking condition in the smoker group, compared to baseline scans in non-smokers, in the cingulate cortex, thalamus, ventral basal ganglia, and amygdala. These reductions were reversed during the average nicotine condition in the thalamus, ventral basal ganglia and amygdala. These data point to both the feasibility of simultaneously examining opioid and DA neurotransmission responses to smoking in humans, as well as to the need to examine non-nicotine aspects of smoking to more fully understand the behavioral effects of this drug.
authors.affiliation: Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-0720, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Scott
authors.forename: Edward F
authors.initials: EF
authors.lastname: Domino
authors.forename: Mary M
authors.initials: MM
authors.lastname: Heitzeg
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Lisong
authors.initials: L
authors.lastname: Ni
authors.forename: Sally
authors.initials: S
authors.lastname: Guthrie
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D004298:Dopamine / Q000378:metabolism; D005283:Fentanyl / Q000031:analogs & derivatives; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D018847:Opioid Peptides / Q000378:metabolism; D049268:Positron-Emission Tomography; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D012907:Smoking / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D002250:Carbon Radioisotopes; D018722:Nicotinic Agonists; D018847:Opioid Peptides; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D020891:Raclopride; D009538:Nicotine; C017114:carfentanil; D005283:Fentanyl; D004298:Dopamine