Serotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PET.

TitleSerotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PET.
Publication TypeJournal Article
Year of Publication2009
AuthorsChristian, BT, Fox, AS, Oler, JA, Vandehey, NT, Murali, D, Rogers, J, Oakes, TR, Shelton, SE, Davidson, RJ, Kalin, NH
JournalNeuroimage
Volume47
Issue4
Pagination1230-6
Date Published2009 Oct 01
ISSN1095-9572
KeywordsAniline Compounds, Animals, Brain, Carbon Radioisotopes, Female, Genotype, Humans, Macaca mulatta, Male, Positron-Emission Tomography, Protein Binding, Radiopharmaceuticals, Serotonin Plasma Membrane Transport Proteins, Sulfides, Tissue Distribution
Abstract

UNLABELLED: 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.

DOI10.1016/j.neuroimage.2009.05.090
Alternate JournalNeuroimage
PubMed ID19505582
PubMed Central IDPMC2798593
Grant ListP51 RR000167 / RR / NCRR NIH HHS / United States
P50 MH084051-02 / MH / NIMH NIH HHS / United States
P50 MH084051 / MH / NIMH NIH HHS / United States
P50 MH052354-080003 / MH / NIMH NIH HHS / United States
P50 MH069315-050002 / MH / NIMH NIH HHS / United States
R01 MH046729-08 / MH / NIMH NIH HHS / United States
MH069315 / MH / NIMH NIH HHS / United States
R01 MH081884 / MH / NIMH NIH HHS / United States
RR000167 / RR / NCRR NIH HHS / United States
MH046729 / MH / NIMH NIH HHS / United States
P50 MH069315 / MH / NIMH NIH HHS / United States
P51 OD011106 / OD / NIH HHS / United States
R01 MH046729 / MH / NIMH NIH HHS / United States
MH84051 / MH / NIMH NIH HHS / United States
MH052354 / MH / NIMH NIH HHS / United States