Though the correlation estimates in cortex should be interpreted with caution due to poor signal to noise ratio of MADAM binding in these regions, it suggests a link between two key proteins involved in the regulation of synaptic serotonin levels. In most cortical regions the correlation was strong, e.g., frontal cortex, r(15) = 0.64, p = 0.01 and parietal cortex, r(15) = 0.8, p = 0.0002 while in most subcortical regions, negligible correlations was observed. AZ10419369 and MADAM binding was positively correlated in all examined brain regions.
The binding potential was calculated for a set of brain regions, and the correlations between the binding estimates of the two radioligands were studied. Seventeen healthy individuals were examined with PET twice, using the radioligands AZ10419369 and MADAM for quantification of the 5-HT 1B receptor and the 5-HT transporter, respectively. Here we will for the first time in vivo examine the relationship between 5-HT 1B receptors and serotonin transporters in the living human brain. Evidence of such coupling could translate to an untapped therapeutic potential in augmenting the effect of selective serotonin reuptake inhibitors through pharmacological modulation of 5-HT 1B receptors.
Animal studies have shown a regulatory link between the two proteins. Synaptic serotonin levels in the brain are regulated by active transport into the bouton by the serotonin transporter, and by autoreceptors, such as the inhibitory serotonin (5-HT) 1B receptor which, when activated, decreases serotonin release.
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