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

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 serotonin2A(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 healthyhumansubjects. Fifty-six healthyhumansubjects with ameanage 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.Aninverted 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-HT 2A receptor and SERT binding could be driven by the projection output from the raphe nuclei, but other explanations are also at hand. Copyright © 2010 the authors.