TY - JOUR
T1 - A nonlinear relationship between cerebral serotonin transporter and 5-HT(2A) receptor binding: an in vivo molecular imaging study in humans
AU - Erritzoe, David
AU - Holst, Klaus
AU - Frokjaer, Vibe G
AU - Licht, Cecilie Löe
AU - Kalbitzer, Jan
AU - Nielsen, Finn A
AU - Svarer, Claus
AU - Madsen, Jacob
AU - Knudsen, Gitte
N1 - Keywords: Adult; Aged; Aged, 80 and over; Benzylamines; Binding, Competitive; Brain Chemistry; Brain Mapping; Cerebral Cortex; Computer Simulation; Female; Humans; Ketanserin; Male; Middle Aged; Positron-Emission Tomography; Radioisotopes; Radioligand Assay; Receptor, Serotonin, 5-HT2A; Serotonin; Serotonin Plasma Membrane Transport Proteins; Synaptic Transmission; Young Adult
PY - 2010/3/3
Y1 - 2010/3/3
N2 - 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.
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 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.
U2 - 10.1523/JNEUROSCI.2852-09.2010
DO - 10.1523/JNEUROSCI.2852-09.2010
M3 - Journal article
C2 - 20203198
SN - 0270-6474
VL - 30
SP - 3391
EP - 3397
JO - The Journal of neuroscience : the official journal of the Society for Neuroscience
JF - The Journal of neuroscience : the official journal of the Society for Neuroscience
IS - 9
ER -
