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

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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]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. Synapse 41:275–284, 2001.