Sex differences in [123I]β-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers

Julie K. Staley, Suchitra Krishnan-Sarin, Sami Zoghbi, Gilles Tamagnan, Masahiro Fujita, John P. Seibyl, Paul K. Maciejewski, Stephanie O'Malley, Robert B. Innis

Research output: Contribution to journalArticlepeer-review

233 Scopus citations


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]β-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]β-CIT uptake was not altered by smoking, whereas brainstem [123I]β-CIT uptake was modestly higher (10%) in smokers vs. nonsmokers. When subgrouped by sex, regardless of smoking status, [123I]β-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]β-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.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
Issue number4
StatePublished - Sep 15 2001


  • Brain
  • Female
  • Male
  • Nicotine
  • Reuptake
  • Single photon emission computed tomography

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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