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Effects of Smoking Cessation on Presynaptic Dopamine Function of Addicted Male Smokers

Published:November 19, 2015DOI:https://doi.org/10.1016/j.biopsych.2015.11.009

      Abstract

      Background

      There is evidence of abnormal cerebral dopamine transmission in nicotine-dependent smokers, but it is unclear whether dopaminergic abnormalities are due to acute nicotine abuse or whether they persist with abstinence. We addressed this question by conducting longitudinal positron emission tomography (PET) examination of smokers before and after 3 months of abstinence.

      Methods

      We obtained baseline 6-[18F]fluoro-L-DOPA (FDOPA)-PET scans in 15 nonsmokers and 30 nicotine-dependent smokers, who either smoked as per their usual habit or were in acute withdrawal. All smokers then underwent cessation treatment, and successful abstainers were re-examined by FDOPA-PET after 3 months of abstinence (n = 15). Uptake of FDOPA was analyzed using a steady-state model yielding estimates of the dopamine synthesis capacity (K); the turnover of tracer dopamine formed in living brain (kloss); and the tracer distribution volume (Vd), which is an index of dopamine storage capacity.

      Results

      Compared with nonsmokers, K was 15% to 20% lower in the caudate nuclei of consuming smokers. Intraindividual comparisons of consumption and long-term abstinence revealed significant increases in K in the right dorsal and left ventral caudate nuclei. Relative to acute withdrawal, Vd significantly decreased in the right ventral and dorsal caudate after prolonged abstinence. Severity of nicotine dependence significantly correlated with dopamine synthesis capacity and dopamine turnover in the bilateral ventral putamen of consuming smokers.

      Conclusions

      The results suggest a lower dopamine synthesis capacity in nicotine-dependent smokers that appears to normalize with abstinence. Further investigations are needed to clarify the role of dopamine in nicotine addiction to help develop smoking prevention and cessation treatments.

      Keywords

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      Linked Article

      • A Need for Longitudinal Studies in the Addiction Field
        Biological PsychiatryVol. 80Issue 3
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          A hallmark of drug addiction, including tobacco smoking addiction, is a dysfunctional dopaminergic reward system. Positron emission tomography (PET) neuroimaging has been used to identify persistent deficits in the availability of striatal dopamine D2/D3 receptors across various addictions, including alcohol, cocaine, heroin, amphetamine, and nicotine (1). These findings suggest that addiction leads to a chronic downregulation in the number of dopamine D2/D3 receptors. In addition, a “blunted” dopamine response to an amphetamine challenge has been documented in both alcohol-dependent (2) and cocaine-dependent (3) individuals several weeks after the last drug use compared to healthy controls; the more blunted the response, the worse the treatment outcome (3).
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