Lack of age-dependent decrease in dopamine D 3 receptor availability: A [11C]-(+)-PHNO and [11C]-raclopride positron emission tomography study

Abstract

Positron emission tomography with antagonist radiotracers has showed that striatal dopamine D 2/3 receptor (D 2/3 R) availability decreases with age. However, no study has specifically assessed whether D 2/3 R availability decreases with age in healthy persons as measured with agonist radiotracers. Moreover, it is unknown whether D 3 R availability changes with age in healthy humans. Thus, we explored the relationship between age and D 2/3 R availability in healthy humans using the D 3 receptor (D 3 R)-preferential agonist radiotracer [11C]-(+)-PHNO (n=72, mean±s.d. age=40±15, range=18 to 73) and the antagonist [11C]-Raclopride (n=70, mean±s.d. age =40±14, range=18 to 73) (both, n=33). The contribution of D 3 R to the [11C]-(+)-PHNO signal varies across regions of interest; the substantia nigra and hypothalamus represent D 3 R-specific regions, the ventral pallidum, globus pallidus, and ventral striatum represent D 2/3 R-mixed regions, and the caudate and putamen represent D 2 receptor (D 2 R)-specific regions. With [11C]-(+)-PHNO, a negative correlation was observed between age and nondisplaceable binding potential (BP ND) in the caudate (r(70)=-0.32, P=0.005). No correlations were observed in the other regions. With [11C]-Raclopride, negative correlations were observed between age and BP ND 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 D 2 R availability, these findings suggest that D 3 R availability does not change with age.