title: Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers.
abstract: Nicotine and other constituents of tobacco smoke elevate dopamine (DA) and serotonin (5-HT) levels in brain and may cause homeostatic adaptations in DA and 5-HT transporters. Since sex steroids alter DA and 5-HT transporter expression, the effects of smoking on DA and 5-HT transporter availability may differ between sexes. In the present study, DA and 5-HT transporter availabilities were quantitated using single photon emission computed tomography (SPECT) imaging approximately 22 h after bolus administration of [123I]beta-CIT, an analog of cocaine which labels DA and 5-HT transporters. Forty-two subjects including 21 pairs of age-, race-, and gender-matched healthy smokers and nonsmokers (12 female and 9 male pairs) were imaged. Regional uptake was assessed by the outcome measures, V3", which is the ratio of specific (i.e., ROI-cerebellar activity) to nondisplaceable (cerebellar) activity, and V3, the ratio of specific to free plasma parent. Overall, striatal and diencephalic [123I]beta-CIT uptake was not altered by smoking, whereas brainstem [123I]beta-CIT uptake was modestly higher (10%) in smokers vs. nonsmokers. When subgrouped by sex, regardless of smoking status, [123I]beta-CIT uptake was higher in the striatum (10%), diencephalon (15%), and brainstem (15%) in females vs. males. The sex*smoking interaction was not significant in the striatum, diencephalon, or brainstem, despite the observation of 20% higher brainstem [123I]beta-CIT uptake in male smokers vs. nonsmokers and less than a 5% difference between female smokers and nonsmokers. The results demonstrate higher DA and 5-HT transporter availability in females vs. males and no overall effect of smoking with the exception of a modest elevation in brainstem 5-HT transporters in male smokers. Although these findings are preliminary and need validation with a more selective 5-HT transporter radiotracer, the results suggest that brainstem 5-HT transporters may be regulated by smoking in a sex-specific manner.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, and VA Connecticut Healthcare System, West Haven, Connecticut 06516, USA. julie.staley@yale.edu
authors.forename: J K
authors.initials: JK
authors.lastname: Staley
authors.forename: S
authors.initials: S
authors.lastname: Krishnan-Sarin
authors.forename: S
authors.initials: S
authors.lastname: Zoghbi
authors.forename: G
authors.initials: G
authors.lastname: Tamagnan
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: P K
authors.initials: PK
authors.lastname: Maciejewski
authors.forename: S
authors.initials: S
authors.lastname: O'Malley
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D000339:Affect / Q000502:physiology; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D012727:Sex Characteristics; D012907:Smoking; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine