A Nonlinear Relationship between Cerebral Serotonin Transporter and 5-HT2A Receptor Binding: An In Vivo Molecular Imaging Study in Humans

作者:Erritzoe David*; Holst Klaus; Frokjaer Vibe G; Licht Cecilie L; Kalbitzer Jan; Nielsen Finn A; Svarer Claus; Madsen Jacob; Knudsen Gitte
来源:Journal of Neuroscience, 2010, 30(9): 3391-3397.
DOI:10.1523/JNEUROSCI.2852-09.2010

摘要

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-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 [C-11]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile (DASB) and 5-HT2A receptor binding with [F-18] 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.

  • 出版日期2010-3-3