|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, B. T., Fox A. S., Oler J. A., Vandehey N. T., Murali D., Rogers J., Oakes T. R., Shelton S. E., Davidson R. J., and Kalin N. H. |
|Date Published||2009 Oct 1 |
|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. |
|Alternate Journal||Neuroimage |