PT  - JOURNAL ARTICLE
AU  - Erritzoe, David
AU  - Holst, Klaus
AU  - Frokjaer, Vibe G.
AU  - Licht, Cecilie L.
AU  - Kalbitzer, Jan
AU  - Nielsen, Finn Å.
AU  - Svarer, Claus
AU  - Madsen, Jacob
AU  - Knudsen, Gitte M.
TI  - A Nonlinear Relationship between Cerebral Serotonin Transporter and 5-HT<sub>2A</sub> Receptor Binding: An <em>In Vivo</em> Molecular Imaging Study in Humans
AID  - 10.1523/JNEUROSCI.2852-09.2010
DP  - 2010 Mar 03
TA  - The Journal of Neuroscience
PG  - 3391--3397
VI  - 30
IP  - 9
4099  - http://www.jneurosci.org/content/30/9/3391.short
4100  - http://www.jneurosci.org/content/30/9/3391.full
SO  - J. Neurosci.2010 Mar 03; 30
AB  - 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 [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.