title: Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers.
abstract: The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward.
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, United States of America.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kuwabara
authors.affiliation: Nicotine Psychopharmacology, National Institute on Drug Abuse, Intramural Research Program, Baltimore, United States of America; Department of Psychiatry, Johns Hopkins University, Baltimore, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Heishman
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, United States of America.
authors.forename: James R
authors.initials: JR
authors.lastname: Brasic
authors.affiliation: Nicotine Psychopharmacology, National Institute on Drug Abuse, Intramural Research Program, Baltimore, United States of America.
authors.forename: Carlo
authors.initials: C
authors.lastname: Contoreggi
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, United States of America.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascella
authors.affiliation: Nicotine Psychopharmacology, National Institute on Drug Abuse, Intramural Research Program, Baltimore, United States of America.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Mackowick
authors.affiliation: Nicotine Psychopharmacology, National Institute on Drug Abuse, Intramural Research Program, Baltimore, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Taylor
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, United States of America.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rousset
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Willis
authors.affiliation: Chemistry and Drug Metabolism Sections, National Institute on Drug Abuse, Intramural Research Program, Baltimore, United States of America.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
authors.affiliation: Chemistry and Drug Metabolism Sections, National Institute on Drug Abuse, Intramural Research Program, Baltimore, United States of America.
authors.forename: Marta
authors.initials: M
authors.lastname: Concheiro
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Wand
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, United States of America; Department of Psychiatry, Johns Hopkins University, Baltimore, United States of America; Department of Neuroscience, Johns Hopkins University, Baltimore, United States of America.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: National Institute on Drug Abuse, Rockville, United States of America.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000097:blood; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012201:Reward; D057566:Self Report; D012720:Severity of Illness Index; D012907:Smoking / Q000378:metabolism / Q000523:psychology; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002250:Carbon Radioisotopes; D018722:Nicotinic Agonists; C485764:OPRM1 protein, human; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu; D009538:Nicotine; C017114:carfentanil; D005283:Fentanyl