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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Article info
Publication history
Published online: November 19, 2015
Accepted:
November 11,
2015
Received in revised form:
October 25,
2015
Received:
May 5,
2015
Identification
Copyright
© 2016 Society of Biological Psychiatry.
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- A Need for Longitudinal Studies in the Addiction FieldBiological PsychiatryVol. 80Issue 3
- PreviewA 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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