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The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System
Published on: April 25, 2012
Cigarette smoking is associated with levels of the serotonin transporter in the brain: a [11C]DASB PET Study
Paul Faulkner1, Gitte M Knudsen2,3, Vibe G Frokjaer2,3,4
1Department of Psychology, Queen Mary University of London, London, United Kingdom.
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 behaviors and alterations in brain serotonin in humans in vivo.
Methods:
We therefore analyzed existing [11C]DASB PET data from the Cimbi Database to compare the 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 SERT binding (DASB BPND) values in the bilateral and left hippocampus, and a trend toward such in the right hippocampus. Post hoc ANOVAs revealed that current smokers exhibited greater hippocampal DASB BPND than both non-smokers and ex-smokers, while the latter 2 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.
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