Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Sep;59(9):1445-1450.
doi: 10.2967/jnumed.117.206516. Epub 2018 Apr 6.

Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET

Rajiv Radhakrishnan  1 , Nabeel Nabulsi  2 , Edward Gaiser  1 , Jean-Dominique Gallezot  2 , Shannan Henry  2 , Beata Planeta  2 , Shu-Fei Lin  2 , Jim Ropchan  2 , Wendol Williams  1 , Evan Morris  2   3 , Deepak Cyril D'Souza  1 , Yiyun Huang  2 , Richard E Carson  2   3 , David Matuskey  4   2
Affiliations

Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET

Rajiv Radhakrishnan et al. J Nucl Med. 2018 Sep.

Abstract

Serotonin receptor 6 (5-hydroxytrypamine-6, or 5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C-GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. Methods: Twenty-eight healthy male volunteers (age range, 23-52 y) were scanned with 11C-GSK215083 PET. Time-activity curves in regions of interest were fitted using a multilinear analysis method. Nondisplaceable binding potential (BPND) was calculated using the cerebellum as the reference region and corrected for partial-volume effects. Results: In 5-HT6-rich areas, regional 11C-GSK215083 showed a negative correlation between BPND and age in the caudate (r = -0.41, P = 0.03) (14% change per decade) and putamen (r = -0.30, P = 0.04) (11% change per decade) but not in the ventral striatum or pallidum. A negative correlation with age was also seen in cortical regions (r = -0.41, P = 0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. Conclusion: To our knowledge, this was the first in vivo study on humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.

Keywords: 11C-GSK215083; 5-HT6; PET imaging; age effects; serotonin 6.

PubMed Disclaimer

Figures

FIGURE 1.
FIGURE 1.
Correlation between age and 11C-GSK215083 BPND in caudate (A), putamen (B), and cortical (C) regions.
See this image and copyright information in PMC

References

    1. Yun HM, Rhim H. The serotonin-6 receptor as a novel therapeutic target. Exp Neurobiol. 2011;20:159–168. - PMC - PubMed
    1. Borsini F, Bordi F, Riccioni T. 5-HT6 pharmacology inconsistencies. Pharmacol Biochem Behav. 2011;98:169–172. - PubMed
    1. Hirst WD, Abrahamsen B, Blaney FE, et al. Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling. Mol Pharmacol. 2003;64:1295–1308. - PubMed
    1. Schechter LE, Lin Q, Smith DL, et al. Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466. Neuropsychopharmacology. 2008;33:1323–1335. - PubMed
    1. Hirst WD, Stean TO, Rogers DC, et al. SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models. Eur J Pharmacol. 2006;553:109–119. - PubMed

Publication types

LinkOut - more resources