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

Nicotine and other constituents of tobacco smoke elevate dopamine (DA) and serotonin (5-HT) levels in brain and may cause homeostatic adaptations in D A and 5-HT transporters. Since sex steroids alter DA and 5-HT transporter e xpression, the effects of smoking on DA and 5-HT transporter availability m ay differ between sexes. In the present study, DA and 5-HT transporter avai labilities were quantitated using single photon emission computed tomograph y (SPECT) imaging approximately 22 h after bolus administration of [I-123]b eta -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, V-3", which is the ratio of sp ecific (i.e., ROI-cerebellar activity) to nondisplaceable (cerebellar) acti vity, and V-3, the ratio of specific to free plasma parent. Overall, striat al and diencephalic [I-123] beta -CIT uptake was not altered by smoking, wh ereas brainstem [I-123] beta -CIT uptake was modestly higher (10%) in smoke rs vs. nonsmokers. When subgrouped by sex, regardless of smoking status, [I -123] 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 o bservation of 20% higher brainstem [I-123] beta -CIT uptake in male smokers vs. nonsmokers and less than a 5% difference between female smokers and no nsmokers. The results demonstrate higher DA and 5-HT transporter availabili ty 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. Alth ough these findings are preliminary and need validation with a more selecti ve 5-HT transporter radiotracer, the results suggest that brainstem 5-HT tr ansporters may be regulated by smoking in a sex-specific manner. (C) 2001 W iley-Liss, Inc.