title: A nonlinear relationship between cerebral serotonin transporter and 5-HT(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 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.
authors.affiliation: Neurobiology Research Unit and PET and Cyclotron Unit, University Hospital Rigshospitalet, Copenhagen, Denmark. david@nru.dk
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: Klaus
authors.initials: K
authors.lastname: Holst
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.forename: Cecilie L
authors.initials: CL
authors.lastname: Licht
authors.forename: Jan
authors.initials: J
authors.lastname: Kalbitzer
authors.forename: Finn A
authors.initials: FA
authors.lastname: Nielsen
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.forename: Gitte
authors.initials: G
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001596:Benzylamines / Q000378:metabolism / Q000493:pharmacokinetics; D001667:Binding, Competitive / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011868:Radioisotopes; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D055815:Young Adult
chemical_list: D001596:Benzylamines; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D011868:Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C071983:altanserin; D007650:Ketanserin