Abstract
BackgroundMesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D2-like receptors. Molecular imaging studies of the relationship between DAT availability/dopamine synthesis capacity and active cigarette smoking have shown conflicting results. Through the collaboration between 13 SPECT centres located in 10 different European countries, a database of FP-CIT-binding in healthy controls was established. We used the database to test the hypothesis that striatal DAT availability is changed in active smokers compared to non-smokers and ex-smokers.MethodsA total of 129 healthy volunteers were included. Subjects were divided into three categories according to past and present tobacco smoking: (1) non-smokers (n = 64), (2) ex-smokers (n = 39) and (3) active smokers (n = 26). For imaging of the DAT availability, we used [123I]FP-CIT (DaTSCAN) and single photon emission computed tomography (SPECT). Data were collected in collaboration between 13 SPECT centres located in 10 different European countries. The striatal measure of DAT availability was analyzed in a multiple regression model with age, SPECT centre and smoking as predictor.ResultsThere was no statistically significant difference in DAT availability between the groups of active smokers, ex-smokers and non-smokers (p = 0.34). Further, we could not demonstrate a significant association between striatal DAT and the number of cigarettes per day or total lifetime cigarette packages in smokers and ex-smokers.ConclusionOur results do not support the hypothesis that large differences in striatal DAT availability are present in smokers compared to ex-smokers and healthy volunteers with no history of smoking.
Highlights
Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs
Such an effect of 5% to 10% is similar to the testretest variability of molecular imaging techniques using positron emission tomography (PET) and single photon emission computed tomography (SPECT) [20,21,22] and may be difficult to demonstrate in PET and SPECT studies using small data samples
Residual analysis revealed that a log transformation of the dopamine transporter (DAT) measurements was favorable
Summary
Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The reduction in D2/3 binding upon smoking compared to the baseline condition is modest (5% to 10%) in these studies compared to that following cocaine (20% to 30%) [16] and amphetamine [17,18,19] Such an effect of 5% to 10% is similar to the testretest variability of molecular imaging techniques using PET and SPECT [20,21,22] and may be difficult to demonstrate in PET and SPECT studies using small data samples. Two SPECT studies failed to demonstrate changes in striatal dopamine D2/3 receptor availability in smokers compared to non-smokers [27,28]
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