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

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-HT_2A in the cortex. <b>Methods:</b> 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 (<i>BP</i>_ND) was calculated using the cerebellum as the reference region and corrected for partial-volume effects. <b>Results:</b> In 5-HT₆-rich areas, regional ¹¹C-GSK215083 showed a negative correlation between <i>BP</i>_ND and age in the caudate (<i>r</i> = -0.41, <i>P</i> = 0.03) (14% change per decade) and putamen (<i>r</i> = -0.30, <i>P</i> = 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 (<i>r</i> = -0.41, <i>P</i> = 0.03) (7% change per decade), consistent with the literature on 5-HT_2A availability. <b>Conclusion:</b> 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 (<i>BP</i>_ND) in the caudate and putamen.