A nonlinear relationship between cerebral serotonin transporter and 5-HT(2A) receptor binding: an in vivo molecular imaging study in humans

David Erritzøe, Klaus Holst, Vibe Gedsø Frøkjær, Cecilie L. Licht, Jan Kalbitzer, Finn Årup Nielsen, Claus Svarer, Jacob Madsen, Gittte Moos Knudsen

AbstractSerotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Within the serotonin transmitter system, both the postsynaptically located serotonin 2A (5-HT2A) receptor and the presynaptic serotonin transporter (SERT) are sensitive to chronic changes in cerebral 5-HT levels. Additionally, experimental studies suggest that alterations in either the 5-HT2A receptor or SERT level can affect the protein level of the counterpart. The aim of this study was to explore the covariation between cerebral 5-HT2A receptor and SERT in vivo in the same healthy human subjects. Fifty-six healthy human subjects with a mean age of 36 ± 19 years were investigated. The SERT binding was imaged with [11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) and 5-HT2A receptor binding with [18F]altanserin using positron emission tomography. Within each individual, a regional intercorrelation for the various brain regions was seen with both markers, most notably for 5-HT2A receptor binding. An inverted U-shaped relationship between the 5-HT2A receptor and the SERT binding was identified. The observed regional intercorrelation for both the 5-HT2A receptor and the SERT cerebral binding suggests that, within the single individual, each marker has a set point adjusted through a common regulator. A quadratic relationship between the two markers is consistent with data from experimental studies of the effect on SERT and 5-HT2A receptor binding of chronic changes in 5-HT levels. That is, the observed association between the 5-HT2A receptor and SERT binding could be driven by the projection output from the raphe nuclei, but other explanations are also at hand.
KeywordsMolecular neuroimaging, positron emission tomography
TypeJournal paper [With referee]
JournalThe Journal of Neuroscience
Year2010    Month March    Vol. 30    No. 9    pp. 3391-3397
Publication linkhttp://www.jneurosci.org/cgi/content/abstract/30/9/3391
BibTeX data [bibtex]
IMM Group(s)Intelligent Signal Processing

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