title: Sex differences in the brain's dopamine signature of cigarette smoking.
abstract: Cigarette smoking is a major public health danger. Women and men smoke for different reasons and cessation treatments, such as the nicotine patch, are preferentially beneficial to men. The biological substrates of these sex differences are unknown. Earlier PET studies reported conflicting findings but were each hampered by experimental and/or analytical limitations. Our new image analysis technique, lp-ntPET (Normandin et al., 2012; Morris et al., 2013; Kim et al., 2014), has been optimized for capturing brief (lasting only minutes) and highly localized dopaminergic events in dynamic PET data. We coupled our analysis technique with high-resolution brain scanning and high-frequency motion correction to create the optimal experiment for capturing and characterizing the effects of smoking on the mesolimbic dopamine system in humans. Our main finding is that male smokers smoking in the PET scanner activate dopamine in the right ventral striatum during smoking but female smokers do not. This finding-men activating more ventrally than women-is consistent with the established notion that men smoke for the reinforcing drug effect of cigarettes whereas women smoke for other reasons, such as mood regulation and cue reactivity. lp-ntPET analysis produces a novel multidimensional endpoint: voxel-level temporal patterns of neurotransmitter release ("DA movies") in individual subjects. By examining these endpoints quantitatively, we demonstrate that the timing of dopaminergic responses to cigarette smoking differs between men and women. Men respond consistently and rapidly in the ventral striatum whereas women respond faster in a discrete subregion of the dorsal putamen.
authors.affiliation: Yale PET Center, Department of Diagnostic Radiology, Department of Psychiatry, and.
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.affiliation: Yale PET Center, Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06519.
authors.forename: Shuo
authors.identifier: http://orcid.org/0000-0003-3129-1333
authors.initials: S
authors.lastname: Wang
authors.affiliation: Yale PET Center, Department of Diagnostic Radiology.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, and.
authors.forename: Erin
authors.initials: E
authors.lastname: McGovern
authors.affiliation: Yale PET Center, Department of Diagnostic Radiology.
authors.forename: Nabeel
authors.identifier: http://orcid.org/0000-0001-8129-0051
authors.initials: N
authors.lastname: Nabulsi
authors.affiliation: Yale PET Center, Department of Diagnostic Radiology.
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.affiliation: Yale PET Center, Department of Diagnostic Radiology.
authors.forename: David
authors.initials: D
authors.lastname: Labaree
authors.affiliation: Department of Diagnostic Radiology, Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06519.
authors.forename: Hemant D
authors.initials: HD
authors.lastname: Tagare
authors.affiliation: Yale PET Center, Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06519.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Sullivan
authors.affiliation: Yale PET Center, Department of Diagnostic Radiology, Department of Psychiatry, and Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06519 evan.morris@yale.edu.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Morris
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D012727:Sex Characteristics; D012907:Smoking / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004298:Dopamine
keywords: PET; dopamine; raclopride; reinforcement; sex differences; tobacco smoking