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

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A nonlinear relationship between cerebral serotonin transporter and 5-HT(2A) receptor binding: an in vivo molecular imaging study in humans.
J Neurosci. 2010 Mar 3;30(9):3391-7
Authors: Erritzoe D, Holst K, Frokjaer VG, Licht CL, Kalbitzer J, Nielsen FA, Svarer C, Madsen J, Knudsen G
Abstract
Serotonergic 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-HT(2A)) 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-HT(2A) 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-HT(2A) 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 [(11)C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) and 5-HT(2A) receptor binding with [(18)F]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-HT(2A) receptor binding. An inverted U-shaped relationship between the 5-HT(2A) receptor and the SERT binding was identified. The observed regional intercorrelation for both the 5-HT(2A) 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-HT(2A) receptor binding of chronic changes in 5-HT levels. That is, the observed association between the 5-HT(2A) receptor and SERT binding could be driven by the projection output from the raphe nuclei, but other explanations are also at hand.
PMID: 20203198 [PubMed – indexed for MEDLINE]
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