title: Sex Differences in Midbrain Dopamine D2-Type Receptor Availability and Association with Nicotine Dependence.
abstract: Women differ from men in smoking-related behaviors, among them a greater difficulty in quitting smoking. Unlike female smokers, male smokers have lower striatal dopamine D2-type receptor availability (binding potential, BPND) than nonsmokers and exhibit greater smoking-induced striatal dopamine release. Because dopamine D2-type autoreceptors in the midbrain influence striatal dopamine release, a function that has been linked to addiction, we tested for sex differences in midbrain dopamine D2-type receptor BPND and in relationships between midbrain BPND, nicotine dependence and striatal dopamine D2-type receptor BPND. Positron emission tomography was used with [18F]fallypride to measure BPND in a midbrain region, encompassing the substantia nigra and ventral tegmental area, in 18 daily smokers (7 women, 11 men) and 19 nonsmokers (10 women, 9 men). A significant sex-by-group interaction reflected greater midbrain BPND in female but not male smokers than in corresponding nonsmokers (F1, 32=5.089, p=0.03). Midbrain BPND was positively correlated with BPND in the caudate nucleus and putamen in nonsmokers and female smokers but not in male smokers and with nicotine dependence in female but not in male smokers. Striatal BPND was correlated negatively with nicotine dependence and smoking exposure. These findings extend observations on dopamine D2-type receptors in smokers and suggest a sex difference in how midbrain dopamine D2-type autoreceptors influence nicotine dependence.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.|Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Petersen
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Department Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Robertson
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.|The Brain Research Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Dean
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Department of Physics, University of California Irvine, Irvine, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.|Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Department Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.|The Brain Research Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001549:Benzamides / Q000493:pharmacokinetics; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012727:Sex Characteristics; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000473:pathology*; D055815:Young Adult
chemical_list: D001549:Benzamides; D017448:Receptors, Dopamine D2; D019788:Fluorodeoxyglucose F18; C574003:fallypride