Dopamine D(1), D(2), D(3) Receptors, Vesicular Monoamine Transporter Type-2 (VMAT2) and Dopamine Transporter (DAT) Densities in Aged Human Brain

The dopamine D(1), D(2), D(3) receptors, vesicular monoamine transporter type-2 (VMAT2), and dopamine transporter (DAT) densities were measured in 11 aged human brains (aged 77–107.8, mean: 91 years) by quantitative autoradiography. The density of D(1) receptors, VMAT2, and DAT was measured using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively. The density of D(2) and D(3) receptors was calculated using the D(3)-preferring radioligand, [(3)H]WC-10 and the D(2)-preferring radioligand [(3)H]raclopride using a mathematical model developed previously by our group. Dopamine D(1), D(2), and D(3) receptors are extensively distributed throughout striatum; the highest density of D(3) receptors occurred in the nucleus accumbens (NAc). The density of the DAT is 10–20-fold lower than that of VMAT2 in striatal regions. Dopamine D(3) receptor density exceeded D(2) receptor densities in extrastriatal regions, and thalamus contained a high level of D(3) receptors with negligible D(2) receptors. The density of dopamine D(1) linearly correlated with D(3) receptor density in the thalamus. The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density. D(3) receptor and VMAT2 densities were in similar level between the aged human and aged rhesus brain samples, whereas aged human brain samples had lower range of densities of D(1) and D(2) receptors and DAT compared with the aged rhesus monkey brain. The differential density of D(3) and D(2) receptors in human brain will be useful in the interpretation of PET imaging studies in human subjects with existing radiotracers, and assist in the validation of newer PET radiotracers having a higher selectivity for dopamine D(2) or D(3) receptors.