Dopamine D1 D2 D3 Receptors Vesicular Monoamine Transporter Type-2 (VMAT2) and Dopamine Transporter (DAT) Densities in Aged Human Brain

摘要

The dopamine D1, D2, D3 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 D1 receptors, VMAT2, and DAT was measured using [³H], [³H]dihydrotetrabenazine, and [³H]WIN35428, respectively. The density of D2 and D3 receptors was calculated using the D3-preferring radioligand, [³H]>WC-10 and the D2-preferring radioligand [³H]raclopride using a mathematical model developed previously by our group. Dopamine D1, D2, and D3 receptors are extensively distributed throughout striatum; the highest density of D3 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 D3 receptor density exceeded D2 receptor densities in extrastriatal regions, and thalamus contained a high level of D3 receptors with negligible D2 receptors. The density of dopamine D₁ linearly correlated with D₃ receptor density in the thalamus. The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density. D₃ 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 D₁ and D₂ receptors and DAT compared with the aged rhesus monkey brain. The differential density of D₃ and D₂ 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 D₂ or D₃ receptors.