Serotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PET.
The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression. The nonhuman primate has been used as a model to study anxiety-related mechanisms in humans based upon similarities in behavior and the presence of a similar 5-HT transporter gene polymorphism. Stressful and threatening contexts in the nonhuman primate model have revealed 5-HT transporter genotype dependent differences in regional glucose metabolism. Using the rhesus monkey, we examined the extent to which serotonin transporter genotype is associated with 5-HT transporter binding in brain regions implicated in emotion-related pathology.


METHODS
Genotype data and high resolution PET scans were acquired in 29 rhesus (Macaca mulatta) monkeys. [C-11]DASB dynamic PET scans were acquired for 90 min in the anesthetized animals and images of distribution volume ratio (DVR) were created to serve as a metric of 5-HT transporter binding for group comparison based on a reference region method of analysis. Regional and voxelwise statistical analysis were performed with corrections for anatomical differences in gray matter probability, sex, age and radioligand mass.


RESULTS
There were no significant differences when comparing l/l homozygotes with s-carriers in the regions of the brain implicated in anxiety and mood related illnesses (amygdala, striatum, thalamus, raphe nuclei, temporal and prefrontal cortex). There was a significant sex difference in 5-HT transporter binding in all regions with females having 18%-28% higher DVR than males.


CONCLUSIONS
Because these findings are consistent with similar genotype findings in humans, this further strengthens the use of the rhesus model for studying anxiety-related neuropathologies.
Christian
B T
BT
Department of Psychiatry, Harlow Primate Center, University of Wisconsin-Madison, USA. bchristian@wisc.edu
Fox
A S
AS
Oler
J A
JA
Vandehey
N T
NT
Murali
D
D
Rogers
J
J
Oakes
T R
TR
Shelton
S E
SE
Davidson
R J
RJ
Kalin
N H
NH
D000814:Aniline Compounds / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides