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Area of Science:

  • Neuroscience
  • Radiochemistry
  • Gerontology

Background:

  • Previous studies using antagonist radiotracers indicated a decline in striatal dopamine D2/3 receptor (D2/3R) availability with age.
  • The age-related changes in D2/3R availability using agonist radiotracers and the specific changes in dopamine D3 receptor (D3R) availability in healthy humans remained uncharacterized.

Purpose of the Study:

  • To investigate the relationship between aging and dopamine D2/3 receptor availability in healthy humans.
  • To differentiate age-related changes in D2 receptor (D2R) and D3 receptor (D3R) availability using specific radiotracers.

Main Methods:

  • Positron emission tomography (PET) scans were performed on healthy participants (n=72 for [(11)C]-(+)-PHNO, n=70 for [(11)C]-Raclopride).
  • The D3R-preferential agonist radiotracer [(11)C]-(+)-PHNO and the D2R/D3R antagonist radiotracer [(11)C]-Raclopride were utilized.
  • Nondisplaceable binding potential (BPND) was analyzed in various brain regions, including D3R-specific (substantia nigra, hypothalamus), mixed D2/3R (ventral pallidum, globus pallidus, ventral striatum), and D2R-specific (caudate, putamen) areas.

Main Results:

  • [(11)C]-Raclopride revealed significant negative correlations between age and BPND in the caudate, putamen, and ventral striatum, indicating age-dependent decreases in D2R availability.
  • [(11)C]-(+)-PHNO showed a negative correlation between age and BPND in the caudate, but no significant age-related changes were observed in other regions, including D3R-specific areas.
  • These findings suggest that while D2R availability declines with age, D3R availability remains unchanged in healthy humans.

Conclusions:

  • The age-dependent decrease in striatal dopamine receptor availability is primarily attributed to changes in D2 receptor availability.
  • Dopamine D3 receptor availability does not appear to change significantly with age in healthy individuals.
  • This study differentiates the aging effects on D2R and D3R, providing crucial insights into neurobiological changes associated with aging.