Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study

J Cereb Blood Flow Metab. 2015 Nov;35(11):1812-8. doi: 10.1038/jcbfm.2015.129. Epub 2015 Jun 10.

Abstract

Positron emission tomography with antagonist radiotracers has showed that striatal dopamine D2/3 receptor (D2/3R) availability decreases with age. However, no study has specifically assessed whether D2/3R availability decreases with age in healthy persons as measured with agonist radiotracers. Moreover, it is unknown whether D3R availability changes with age in healthy humans. Thus, we explored the relationship between age and D2/3R availability in healthy humans using the D3 receptor (D3R)-preferential agonist radiotracer [(11)C]-(+)-PHNO (n=72, mean±s.d. age=40±15, range=18 to 73) and the antagonist [(11)C]-Raclopride (n=70, mean±s.d. age =40±14, range=18 to 73) (both, n=33). The contribution of D3R to the [(11)C]-(+)-PHNO signal varies across regions of interest; the substantia nigra and hypothalamus represent D3R-specific regions, the ventral pallidum, globus pallidus, and ventral striatum represent D2/3R-mixed regions, and the caudate and putamen represent D2 receptor (D2R)-specific regions. With [(11)C]-(+)-PHNO, a negative correlation was observed between age and nondisplaceable binding potential (BPND) in the caudate (r(70)=-0.32, P=0.005). No correlations were observed in the other regions. With [(11)C]-Raclopride, negative correlations were observed between age and BPND in the caudate (r(68)=-0.50, P<0.001), putamen (r(68)=-0.41, P<0.001), and ventral striatum (r(68)=-0.43, P<0.001). In conclusion, in contrast with the age-dependent decrease in D2R availability, these findings suggest that D3R availability does not change with age.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aging / physiology*
  • Binding, Competitive / drug effects
  • Brain / diagnostic imaging*
  • Brain Chemistry / physiology*
  • Carbon Radioisotopes
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / metabolism
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Dopamine Agonists / pharmacology
  • Female
  • Globus Pallidus / diagnostic imaging
  • Globus Pallidus / metabolism
  • Healthy Volunteers
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Oxazines*
  • Positron-Emission Tomography / methods*
  • Putamen / diagnostic imaging
  • Putamen / metabolism
  • Raclopride*
  • Radiopharmaceuticals*
  • Receptors, Dopamine D3 / drug effects*
  • Young Adult

Substances

  • Carbon Radioisotopes
  • Dopamine Agonists
  • Oxazines
  • Radiopharmaceuticals
  • Receptors, Dopamine D3
  • naxagolide
  • Raclopride