title: Cocaine cue-induced dopamine release in the human prefrontal cortex.
abstract: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown.
  
  
  
  We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence.
  
  
  
  Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving.
  
  
  
  Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release.
  
  
  
  In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms.
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Michele S
authors.initials: MS
authors.lastname: Milella
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Aryandokht
authors.initials: A
authors.lastname: Fotros
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Paul
authors.initials: P
authors.lastname: Gravel
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Casey
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Kevin
authors.initials: K
authors.lastname: Larcher
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Verhaeghe
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Sylvia M L
authors.initials: SM
authors.lastname: Cox
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Reader
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Alain
authors.initials: A
authors.lastname: Dagher
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King's College London, St. Thomas' Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
mesh_terms: D000328:Adult; D001549:Benzamides; D001931:Brain Mapping; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D066249:Craving / Q000502:physiology*; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D019275:Radiopharmaceuticals
chemical_list: D001549:Benzamides; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C574003:fallypride; C000615276:Fluorine-18; D003042:Cocaine; D004298:Dopamine