Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 30, Issue 10, Pages 1682-1706Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2010.104
Keywords
endogenous neurotransmitter release; positron emission tomography (PET); 5-HT
Categories
Funding
- Danish Council for Strategic Research
- Medical Research Council
- H Lundbeck A/S
- EuroBioFund
- GSK
- Novartis
- Servier
- Janssen
- Lundbeck
- Pfizer
- Wyeth
- Organon
- Gitte M. Knudsen
- MSD
- MRC [G0601461] Funding Source: UKRI
- Medical Research Council [G0601461] Funding Source: researchfish
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Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system. The principles behind visualising fluctuations in neurotransmitters are introduced, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT1A, 5-HT2A, and 5-H-T4 receptors and the serotonin reuptake transporter have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made as to how the selection of targets, radiotracers, challenge paradigms, and experimental design might be optimised to improve our chances of successfully imaging endogenous neurotransmitters in the future. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1682-1706; doi:10.1038/jcbfm.2010.104; published online 28 July 2010
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