A longitudinal [18F]FDOPA-PET study on nicotine addicted patients before and after long-term abstinence

Objectives Previous studies on addiction suggest disturbances in the dopamine transmission system. This [18F]FDOPA-PET investigation aims to detect nicotine related changes during continued smoking, after acute withdrawal, and after long-term abstinence. The latter condition should simulate the situation before the substance-dependent behaviour became apparent. The reversible inlet/outlet model for [18F]FDOPA-PET analysis was applied for characterization of divers presynaptic kinetic parameters.

Methods 30 male nicotine dependent subjects (28.3±7.0 yrs) and 15 non-smoking subjects (27.9±7.5 yrs) were included. Half of the patients underwent a first scan under acute withdrawal the other half under smoking conditions. Afterwards, all patients attended at a smoking cessation program. 16/30 patients remained abstinent for at least 3 months. This group underwent a second [18F]FDOPA scan (124 min., bolus infusion 228±32 MBq [patients]; arterial blood withdrawal; metabolite detection). The reversible inlet/outlet model of Kumakura et al. (2005) was applied in order to obtain the net blood/brain clearance (K), the loss of fluorinated metabolites (kloss), and the total distribution volume (VD).

Results Positive correlations between the dopamine transmission and cognitive performance could be replicated (TMT-B vs. VD in vNC: r=-0.631, p=0.016). Smoking patients showed a reduced dopamine synthesis capacity in particular in the right (-16%, p=0.045) and left ventral caudate nucleus (-16%, p=0.050). The kloss sowed a reduction on trend-level. The long-term smoking cessation, nevertheless, normalized all presynaptic dopaminergic parameters. The state of acute withdrawal showed a tendency toward reduced K and kloss.

Conclusions Ongoing nicotine consumption results in a down-regulation of dopamine-synthesis capacity and turn-over. The complete normalization after 3 months of abstinence, however, was unexpected and does not claim an inefficient dopamine system to be a strong trait toward nicotine dependence.