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

Synapse. 2001 Sep 15;41(4):275-84. doi: 10.1002/syn.1084.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Affect / physiology
  • Brain Stem / diagnostic imaging
  • Brain Stem / metabolism
  • Carrier Proteins / metabolism*
  • Cocaine / analogs & derivatives
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Humans
  • Iodine Radioisotopes
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Radiopharmaceuticals
  • Serotonin Plasma Membrane Transport Proteins
  • Sex Characteristics*
  • Smoking*
  • Tomography, Emission-Computed, Single-Photon*


  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Radiopharmaceuticals
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Cocaine