In vivo correlation of serotonin transporter and 1B receptor availability in the human brain: a PET study

Neuropsychopharmacology. 2022 Sep;47(10):1863-1868. doi: 10.1038/s41386-022-01369-3. Epub 2022 Jul 11.

Abstract

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. Animal studies have shown a regulatory link between the two proteins. 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-HT1B receptors. Here we will for the first time in vivo examine the relationship between 5-HT1B receptors and serotonin transporters in the living human brain. Seventeen healthy individuals were examined with PET twice, using the radioligands [11C]AZ10419369 and [11C]MADAM for quantification of the 5-HT1B receptor and the 5-HT transporter, respectively. The binding potential was calculated for a set of brain regions, and the correlations between the binding estimates of the two radioligands were studied. [11C]AZ10419369 and [11C]MADAM binding was positively correlated in all examined brain regions. 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. Though the correlation estimates in cortex should be interpreted with caution due to poor signal to noise ratio of [11C]MADAM binding in these regions, it suggests a link between two key proteins involved in the regulation of synaptic serotonin levels. Our results indicate a need for further studies to address the functional importance of 5-HT1B receptors in treatment with drugs that inhibit serotonin reuptake.

MeSH terms

  • Animals
  • Brain
  • Humans
  • Positron-Emission Tomography / methods
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Serotonin Plasma Membrane Transport Proteins* / metabolism
  • Serotonin Uptake Inhibitors / metabolism
  • Serotonin Uptake Inhibitors / pharmacology
  • Serotonin* / metabolism

Substances

  • Receptor, Serotonin, 5-HT1B
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Serotonin