Title | Serotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PET. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Christian, BT, Fox, AS, Oler, JA, Vandehey, NT, Murali, D, Rogers, J, Oakes, TR, Shelton, SE, Davidson, RJ, Kalin, NH |
Journal | Neuroimage |
Volume | 47 |
Issue | 4 |
Pagination | 1230-6 |
Date Published | 2009 Oct 01 |
ISSN | 1095-9572 |
Keywords | Aniline 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. |
DOI | 10.1016/j.neuroimage.2009.05.090 |
Alternate Journal | Neuroimage |
PubMed ID | 19505582 |
PubMed Central ID | PMC2798593 |
Grant List | P51 RR000167 / RR / NCRR NIH HHS / United States P50 MH084051-02 / MH / NIMH NIH HHS / United States P50 MH084051 / MH / NIMH NIH HHS / United States R01 MH046729-08 / MH / NIMH NIH HHS / United States MH069315 / MH / NIMH 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 P50 MH052354-080003 / MH / NIMH NIH HHS / United States P50 MH069315-050002 / MH / NIMH NIH HHS / United States R01 MH081884 / MH / NIMH NIH HHS / United States RR000167 / RR / NCRR NIH HHS / United States P50 MH052354 / MH / NIMH NIH HHS / United States MH052354 / MH / NIMH NIH HHS / United States |
Serotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PET.
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