Lack of Age-Dependent Decrease in Dopamine D3 Receptor Availability: A [11C]-(+)-PHNO and [11C]-Raclopride Positron Emission Tomography Study

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 [ 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 D 3 R to the [ 11 C]-(+)-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 [ 11 C]-(+)-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 [ 11 C]-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.