Background: Preclinical work suggests that chronic nicotine/tobacco use is associated with reductions in serotonin within the hippocampus, yet no research has yet shown an association of smoking behaviours and alterations in brain serotonin in humans in vivo.
Methods: We therefore analysed existing [11C]DASB-PET data from the Cimbi Database to compare availability of the serotonin transporter (SERT) in the hippocampus, midbrain (including the raphe) and neocortex of 60 healthy non-smokers, 15 ex-smokers and 11 current smokers who also provided blood samples for determination of plasma tryptophan load. Because SERT availability is considered to be negatively associated with extracellular serotonin levels, we hypothesized that current smokers would exhibit greater SERT availability than ex-smokers and non-smokers.
Results: There was a significant main effect of group on serotonin transporter binding (DASB BPND) values in the bilateral and left hippocampus, and a trend towards such in the right hippocampus. Post-hoc ANOVAs revealed that current smokers exhibited greater hippocampal DASB BPND than both non-smokers and ex-smokers, whilst the latter two groups did not differ. There were no group effects on DASB BPND within the midbrain or global neocortex. Finally, there was no significant group effect on plasma tryptophan load.
Conclusions: This study provides the first in vivo evidence that current smoking may be associated with elevated hippocampal SERT binding - possibly reflecting lower synaptic serotonin concentrations, and that this change may normalize following smoking cessation.
Keywords: 5-HT; Smoking; nicotine; positron emission tomography; serotonin.
© The Author(s) 2025. Published by Oxford University Press on behalf of CINP.